The Amyloid Formation Mechanism in Human IAPP: Dimers Have β-Strand Monomer−Monomer Interfaces
Open accessAbstract
Early oligomerization of human IAPP (hIAPP) is responsible for β-cell death in the pancreas and is increasingly considered a primary pathological process linked to Type II Diabetes (T2D). Yet, the assembly mechanism remains poorly understood, largely due to the inability of conventional techniques to probe distributions or detailed structures of early oligomeric species. Here, we describe the first experimental data on the isolated and unmodified dimers of human (hIAPP) and nonamyloidogenic rat IAPP (rIAPP). The experiments reveal that the human IAPP dimers are more extended than those formed by rat IAPP and likely descend from extended monomers. Independent all-atom molecular dynamics simulations show that rIAPP forms compact helix and coil rich dimers, whereas hIAPP forms β-strand rich dimers that are generally more extended. Also, the simulations reveal that the monomer-monomer interfaces of the hIAPP dimers are dominated by β-strands and that β-strands can recruit coil or helix structured regions during the dimerization process. Our β-rich interface contrasts with an N-terminal helix-to-helix interface proposed in the literature but is consistent with existing experimental data on the self-interaction pattern of hIAPP, mutation effects, and inhibition effects of the N-methylation in the mutation region.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The present work used the AMBER ff96 force field in combination with the OBC2 implicit solvent model, which has been successfully applied to study the association of proteins and peptides by others.
“The present work used the AMBER ff96 force field in combination with the OBC2 implicit solvent model, which has been successfully applied to study the association of proteins and peptides by others.123−125”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [124]
The modeling passage (section labeled Abstract; page unavailable) says this paper used AMBER ff96 with an implicit solvent model it calls IGB=5 to simulate IAPP dimer association. It also reports successful protein and peptide folding with that combination, but our copy does not identify IGB=5 as OBC2 or say that others successfully used it to study association specifically. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Protein Misfolding, Functional Amyloid, and Human Disease
Chiti, F., & Dobson, C. M. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.101304.123901 · Cited by 6,435 · see citing works
Westermark, P., Wernstedt, C., Wilander, E., Hayden, D. W., O'Brien, T. D., & Johnson, K. H. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.11.3881 · Cited by 976 · see citing works
Bernstein, S. L., Dupuis, N., Lazo, N. D., Wyttenbach, T., Condron, M. M., Bitan, G., Teplow, D. B., Shea, J., Ruotolo, B. T., Robinson, C. V., et al. (2009) · Nature Chemistry · doi:10.1038/nchem.247 · Cited by 918 · see citing works
Self-citationLuca, S., Yau, W., Leapman, R. D., & Tycko, R. (2007) · Biochemistry · doi:10.1021/bi701427q · Cited by 579 · see citing works
Molecular simulation of ab initio protein folding for a millisecond folder NTL9(1–39)
Voelz, V. A., Bowman, G., Beauchamp, K., & Pande, V. (2010) · Journal of the American Chemical Society · doi:10.1021/ja9090353 · Cited by 529 · see citing works
Bleiholder, C., Dupuis, N., Wyttenbach, T., & Bowers, M. T. (2010) · Nature Chemistry · doi:10.1038/nchem.945 · Cited by 367 · see citing works
Self-citationConformational transitions of islet amyloid polypeptide (IAPP) in amyloid formation in Vitro
Kayed, R., Bernhagen, J., Greenfield, N. J., Sweimeh, K., Brunner, H., Voelter, W., & Kapurniotu, A. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2646 · Cited by 351 · see citing works
Atomic structure of the cross‐β spine of islet amyloid polypeptide (amylin)
Wiltzius, J. J. W., Sievers, S. A., Sawaya, M. R., Cascio, D., Popov, D., Riekel, C., & Eisenberg, D. S. (2008) · Protein Science · doi:10.1110/ps.036509.108 · Cited by 320 · see citing works
Amyloid Fibril Formation from Full-Length and Fragments of Amylin
Goldsbury, C. S., Goldie, K. N., Pellaud, J., Seelig, J., Frey, P., Müller, S. A., Kistler, J., Cooper, G. J. S., & Aebi, U. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4268 · Cited by 316 · see citing works
Design of a new electrospray ion mobility mass spectrometer
Wyttenbach, T., Kemper, P. R., & Bowers, M. T. (2001) · International Journal of Mass Spectrometry · doi:10.1016/s1387-3806(01)00517-6 · Cited by 278 · see citing works
Self-citationYan, L., Tatarek‐Nossol, M., Velkova, A., Kazantzis, A., & Kapurniotu, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507471103 · Cited by 243 · see citing works
Gas-Phase Conformations: The Ion Mobility/Ion Chromatography Method
Wyttenbach, T., & Bowers, M. T. (2003) · Topics in current chemistry · doi:10.1007/3-540-36113-8_6 · Cited by 224 · see citing works
Self-citationDupuis, N., Wu, C. F., Shea, J., & Bowers, M. T. (2009) · Journal of the American Chemical Society · doi:10.1021/ja903814q · Cited by 215 · see citing works
Self-citationDirect detection of transient α‐helical states in islet amyloid polypeptide
Williamson, J. A., & Miranker, A. D. (2006) · Protein Science · doi:10.1110/ps.062486907 · Cited by 215 · see citing works
Wiltzius, J. J. W., Sievers, S. A., Sawaya, M. R., & Eisenberg, D. S. (2009) · Protein Science · doi:10.1002/pro.145 · Cited by 208 · see citing works
Andreetto, E., Yan, L., Tatarek‐Nossol, M., Velkova, A., Frank, R., & Kapurniotu, A. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.200904902 · Cited by 203 · see citing works
Lin, C., Gurlo, T., Kayed, R., Butler, A. E., Haataja, L., Glabe, C. G., & Butler, P. C. (2007) · Diabetes · doi:10.2337/db06-1579 · Cited by 182 · see citing works
A role for helical intermediates in amyloid formation by natively unfolded polypeptides?
Abedini, A., & Raleigh, D. P. (2009) · Physical Biology · doi:10.1088/1478-3975/6/1/015005 · Cited by 179 · see citing works
Kapurniotu, A., Schmauder, A., & Tenidis, K. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5244 · Cited by 173 · see citing works
A Test on Peptide Stability of AMBER Force Fields with Implicit Solvation
Shell, M. S., Ritterson, R. S., & Dill, K. A. (2008) · The Journal of Physical Chemistry B · doi:10.1021/jp800282x · Cited by 145 · see citing works
Stable and Metastable States of Human Amylin in Solution
Reddy, A. S., Wang, L., Singh, S., Ling, Y. L., Buchanan, L. E., Zanni, M. T., Skinner, J. L., & de Pablo, J. J. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.07.014 · Cited by 116 · see citing works
Tatarek-Nossol, M., Yan, L.-M., Schmauder, A., Tenidis, K., Westermark, G., & Kapurniotu, A. (2005) · Chemistry and Biology · doi:10.1016/j.chembiol.2005.05.010 · Cited by 110 · see citing works
Principles governing oligomer formation in amyloidogenic peptides
Straub, J. E., & Thirumalai, D. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2009.12.017 · Cited by 101 · see citing works
Unfolded-State Dynamics and Structure of Protein L Characterized by Simulation and Experiment
Voelz, V. A., Singh, V. R., Wedemeyer, W. J., Lapidus, L. J., & Pande, V. S. (2010) · Journal of the American Chemical Society · doi:10.1021/ja908369h · Cited by 85 · see citing works
Abedini, A., Singh, G., & Raleigh, D. P. (2005) · Analytical Biochemistry · doi:10.1016/j.ab.2005.11.029 · Cited by 76 · see citing works
Amyloid proteins : the beta sheet conformation and disease
Sipe, J. D. (2005) · Wiley-VCH eBooks · Cited by 72 · see citing works
Spermine Binding to Parkinson’s Protein α-Synuclein and Its Disease-Related A30P and A53T Mutants
Grabenauer, M., Bernstein, S. L., Lee, J. C., Wyttenbach, T., Dupuis, N., Gray, H. B., Winkler, J. R., & Bowers, M. T. (2008) · The Journal of Physical Chemistry B · doi:10.1021/jp801175w · Cited by 62 · see citing works
Self-citationSolution Structures of Rat Amylin Peptide: Simulation, Theory, and Experiment
Reddy, A. S., Wang, L., Lin, Y., Ling, Y. L., Chopra, M., Zanni, M. T., Skinner, J. L., & Pablo, J. J. D. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2009.10.029 · Cited by 51 · see citing works
Rivera, E., Straub, J. E., & Thirumalai, D. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2009.03.039 · Cited by 50 · see citing works
(2005) · Wiley eBooks · doi:10.1002/9783527619344 · Cited by 34 · see citing works
On the Origins of the Weak Folding Cooperativity of a Designed ββα Ultrafast Protein FSD-1
Wu, C. F., & Shea, J. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000998 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 27
- [2]Westermark P Wernstedt C Wilander E Hayden DW Obrien TD Johnson KH P Natl Acad Sci USA 1987 84 11 3881 3885 PMC304980 3035556
- [3]Luca S Yau WM Leapman R Tycko R Biochemistry-Us 2007 46 47 13505 13522 PMC2562526 17979302
- [4]Lin CY Gurlo T Kayed R Butler AE Haataja L Glabe CG Butler PC Diabetes 2007 56 5 1324 1332 17353506
- [5]Dupuis NF Wu C Shea J-E Bowers MT J Am Chem Soc 2009 131 51 18283 18292 19950949 PMC2810149
- [6]Bernstein SL Dupuis NF Lazo ND Wyttenbach T Condron MM Bitan G Teplow DB Shea JE Ruotolo BT Robinson CV Bowers MT Nat Chem 2009 1 4 326 331 20703363 PMC2918915
- [8]Reddy AS Wang L Lin YS Ling Y Chopra M Zanni MT Skinner JL De Pablo JJ Biophys. J 2010 98 3 443 451 20141758 PMC2814214
- [9]Reddy AS Wang L Singh S Ling Y Buchanan L Zanni MT Skinner JL De Pablo JJ Biophys. J 2010 99 7 2208 2216 20923655 PMC3042569
- [10]Kayed R Bernhagen J Greenfield N Sweimeh K Brunner H Voelter W Kapurniotu A J Mol Biol 1999 287 4 781 796 10191146
- [11]Straub J Thirumalai D Curr Opin Struc Biol 2010 20 2 187 195 PMC2854190 20106655
- [12]Abedini A Raleigh D Phys Biol 2009 6 1 015005 19208933 PMC3215505
- [13]Chiti F Dobson CM Annu Rev Biochem 2006 75 333 366 16756495
- [14]Williamson JA Miranker AD Protein Sci 2007 16 1 110 117 17123962 PMC2222845
- [15]Wiltzius JJW Sievers SA Sawaya MR Cascio D Popov D Riekel C Eisenberg D Protein Sci 2008 17 9 1467 1474 18556473 PMC2525530
- [16]Wiltzius J Sievers S Sawaya M Eisenberg D Protein Sci 2009 18 7 1521 1530 19475663 PMC2775219
- [17]Andreetto E Yan L Tatarek-Nossol M Velkova A Frank R Kapurniotu A Angew Chem Int Edit 2010 49 17 3081 3085 20309983
- [18]Kapurniotu A Schmauder A Tenidis K J Mol Biol 2002 315 3 339 350 11786016
- [19]Tatarek-Nossol M Yan L Schmauder A Tenidis K Westermark G Kapurniotu A CHEM BIOL 2005 12 7 797 809 16039527
- [20]Yan LM Tatarek-Nossol M Velkova A Kazantzis A Kapurniotu A P Natl Acad Sci USA 2006 103 7 2046 2051 PMC1413694 16467158
- [21]Abedini A Singh G Raleigh DP Anal Biochem 2006 351 2 181 186 16406209
- [23]Bleiholder C Dupuis NF Wyttenbach T Bowers MT Nat Chem 2011 3 2 172 21258392 PMC3073516
- [24]Shell MS Ritterson R Dill KA J Phys Chem B 2008 112 22 6878 6886 18471007 PMC2699260
- [25]Voelz V Bowman G Beauchamp K Pande V J Am Chem Soc 2010 132 5 1526 1528 20070076 PMC2835335
- [26]Voelz V Singh V Wedemeyer W Lapidus L Pande V J Am Chem Soc 2010 132 13 4702 4709 20218718 PMC2853762
- [27]Wu C Shea J-E PLoS Comput Biol 2010 6 11 e1000998 21124953 PMC2987907
- [28]Grabenauer M Bernstein SL Lee JC Wyttenbach T Dupuis NF Gray HB Winkler JR Bowers MT J Phys Chem B 2008 112 35 11147 11154 18693700 PMC2639767
- [29]Rivera E Straub J Thirumalai D Biophys. J 2009 96 11 4552 4560 19486677 PMC2711455
- [30]Goldsbury C Goldie K Pellaud J Seelig J Frey P Muller SA Kistler J Cooper JS Aebi U J. Struct Biol 2000 130 2–3 352 362 10940238
Cited by
Sorted by citations
Wyttenbach, T., & Bowers, M. T. (2011) · The Journal of Physical Chemistry B · doi:10.1021/jp206867a · Cited by 347 · see citing works
Self-citationImplications of peptide assemblies in amyloid diseases
Ke, P. C., Sani, M., Ding, F., Käkinen, A., Javed, I., Separovic, F., Davis, T. P., & Mezzenga, R. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00372b · Cited by 338 · see citing works
An infrared spectroscopy approach to follow β-sheet formation in peptide amyloid assemblies
Seo, J., Hoffmann, W., Warnke, S., Huang, X., Gewinner, S., Schöllkopf, W., Bowers, M. T., von Helden, G., & Pagel, K. (2016) · Nature Chemistry · doi:10.1038/nchem.2615 · Cited by 238 · see citing works
Self-citationThe Bioinorganic Chemistry of Mammalian Metallothioneins
Krężel, A., & Maret, W. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00371 · Cited by 210 · see citing works
Young, L. M., Cao, P., Raleigh, D. P., Ashcroft, A. E., & Radford, S. E. (2013) · Journal of the American Chemical Society · doi:10.1021/ja406831n · Cited by 190 · see citing works
Adding a new separation dimension to MS and LC–MS: What is the utility of ion mobility spectrometry?
D’Atri, V., Causon, T. J., Hernandez‐Alba, O., Mutabazi, A., Veuthey, J., Cianférani, S., & Guillarme, D. (2017) · Journal of Separation Science · doi:10.1002/jssc.201700919 · Cited by 185 · see citing works
Effects of in vivo conditions on amyloid aggregation
Owen, M. C., Gnutt, D., Gao, M., Wärmländer, S. K. T. S., Jarvet, J., Gräslund, A., Winter, R., Ebbinghaus, S., & Strodel, B. (2019) · Chemical Society Reviews · doi:10.1039/c8cs00034d · Cited by 179 · see citing works
Qiao, Q., Bowman, G. R., & Huang, X. (2013) · Journal of the American Chemical Society · doi:10.1021/ja403147m · Cited by 182 · see citing works
Islet amyloid: From fundamental biophysics to mechanisms of cytotoxicity
Cao, P., Marek, P., Noor, H., Patsalo, V., Tu, L., Wang, H., Abedini, A., & Raleigh, D. P. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.01.046 · Cited by 178 · see citing works
Simulation Studies of Amyloidogenic Polypeptides and Their Aggregates
Ilie, I. M., & Caflisch, A. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00731 · Cited by 177 · see citing works
Amyloidogenic peptide oligomer accumulation in autophagy-deficient β cells induces diabetes
Kim, J., Cheon, H., Jeong, Y. T., Quan, W., Kim, K. H., Cho, J. M., Lim, Y.-M., Oh, S. H., Jin, S., Kim, J. H., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69625 · Cited by 157 · see citing works
Pathways of Amyloid-β Aggregation Depend on Oligomer Shape
Barz, B., Liao, Q., & Strodel, B. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b10343 · Cited by 144 · see citing works
2DIR Spectroscopy of Human Amylin Fibrils Reflects Stable β-Sheet Structure
Wang, L., Middleton, C. T., Singh, S., Reddy, A. S., Woys, A. M., Strasfeld, D. B., Marek, P., Raleigh, D. P., de Pablo, J. J., Zanni, M. T., et al. (2011) · Journal of the American Chemical Society · doi:10.1021/ja204035k · Cited by 119 · see citing works
Aggregation of islet amyloid polypeptide: from physical chemistry to cell biology
Cao, P., Abedini, A., & Raleigh, D. P. (2012) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2012.11.003 · Cited by 119 · see citing works
Chen, S., & Russell, D. H. (2015) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-015-1191-1 · Cited by 113 · see citing works
Simulations of Protein Aggregation: Insights from Atomistic and Coarse-Grained Models
Morriss-Andrews, A., & Shea, J. (2014) · The Journal of Physical Chemistry Letters · doi:10.1021/jz5006847 · Cited by 108 · see citing works
Self-citationRole of β-Hairpin Formation in Aggregation: The Self-Assembly of the Amyloid-β(25–35) Peptide
Larini, L., & Shea, J. (2012) · Biophysical Journal · doi:10.1016/j.bpj.2012.06.027 · Cited by 106 · see citing works
Self-citationDeamidation Accelerates Amyloid Formation and Alters Amylin Fiber Structure
Dunkelberger, E. B., Buchanan, L. E., Marek, P., Cao, P., Raleigh, D. P., & Zanni, M. T. (2012) · Journal of the American Chemical Society · doi:10.1021/ja3039486 · Cited by 104 · see citing works
Pannuzzo, M., Raudino, A., Milardi, D., Rosa, C. L., & Karttunen, M. (2013) · Scientific Reports · doi:10.1038/srep02781 · Cited by 100 · see citing works
Integrating mass spectrometry of intact protein complexes into structural proteomics
Hyung, S., & Ruotolo, B. T. (2012) · PROTEOMICS · doi:10.1002/pmic.201100520 · Cited by 102 · see citing works
An Account of Amyloid Oligomers: Facts and Figures Obtained from Experiments and Simulations
Nagel‐Steger, L., Owen, M. C., & Strodel, B. (2016) · ChemBioChem · doi:10.1002/cbic.201500623 · Cited by 100 · see citing works
Mo, Y., Lei, J., Sun, Y., Zhang, Q., & Wei, G. (2016) · Scientific Reports · doi:10.1038/srep33076 · Cited by 100 · see citing works
Wu, C. F., & Shea, J. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003211 · Cited by 99 · see citing works
Self-citationBleiholder, C., Do, T. D., Wu, C. F., Economou, N. J., Bernstein, S. L., Buratto, S. K., Shea, J., & Bowers, M. T. (2013) · Journal of the American Chemical Society · doi:10.1021/ja406197f · Cited by 93 · see citing works
Self-citationTan, J., Zhang, J., Luo, Y., & Ye, S. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b08537 · Cited by 93 · see citing works
Advances in ion mobility spectrometry–mass spectrometry reveal key insights into amyloid assembly
Woods, L. A., Radford, S. E., & Ashcroft, A. E. (2012) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2012.10.002 · Cited by 93 · see citing works
Liang, G., Zhao, J. W., Yu, X., & Zheng, J. (2013) · Biochemistry · doi:10.1021/bi301525e · Cited by 90 · see citing works
Conformational Distribution and α-Helix to β-Sheet Transition of Human Amylin Fragment Dimer
Qi, R., Luo, Y., Ma, B., Nussinov, R., & Wei, G. (2013) · Biomacromolecules · doi:10.1021/bm401406e · Cited by 87 · see citing works
Carballo‐Pacheco, M., Ismail, A. E., & Strodel, B. (2018) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.8b00579 · Cited by 82 · see citing works
Pavlova, À., Cheng, C., Kinnebrew, M., Lew, J., Dahlquist, F. W., & Han, S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1504415113 · Cited by 79 · see citing works
Susa, A. C., Wu, C. F., Bernstein, S. L., Dupuis, N., Wang, H., Raleigh, D. P., Shea, J., & Bowers, M. T. (2014) · Journal of the American Chemical Society · doi:10.1021/ja504031d · Cited by 76 · see citing works
Self-citationDunkelberger, E. B., Grechko, M., & Zanni, M. T. (2015) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5b07706 · Cited by 76 · see citing works
Chen, S., Chen, L., & Russell, D. H. (2014) · Journal of the American Chemical Society · doi:10.1021/ja5047878 · Cited by 73 · see citing works
General Principles Underpinning Amyloid Structure
Taylor, A. I. P., & Staniforth, R. A. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.878869 · Cited by 68 · see citing works
Pan, J., Han, J., Borchers, C. H., & Konermann, L. (2012) · Biochemistry · doi:10.1021/bi3002049 · Cited by 69 · see citing works
Carufel, C. A. D., Quittot, N., Nguyen, P. T., & Bourgault, S. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201507092 · Cited by 68 · see citing works
Sun, Y., Käkinen, A., Xing, Y., Faridi, P., Nandakumar, A., Purcell, A. W., Davis, T. P., Ke, P. C., & Ding, F. (2019) · Small · doi:10.1002/smll.201805166 · Cited by 67 · see citing works
Jin, Y., Sun, Y., Chen, Y., Lei, J., & Wei, G. (2019) · Physical Chemistry Chemical Physics · doi:10.1039/c9cp01803d · Cited by 67 · see citing works
Bishoyi, A. K., Roham, P. H., Rachineni, K., Save, S. N., Hazari, M. A., Sharma, S., & Kumar, A. (2020) · Biological Chemistry · doi:10.1515/hsz-2020-0174 · Cited by 66 · see citing works
Lao, Z., Chen, Y., Tang, Y., & Wei, G. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00393 · Cited by 63 · see citing works
Nedumpully-Govindan, P., & Ding, F. (2015) · Scientific Reports · doi:10.1038/srep08240 · Cited by 63 · see citing works
Bakou, M., Hille, K., Kracklauer, M., Spanopoulou, A., Frost, C. V., Malideli, E., Yan, L., Caporale, A., Zacharias, M., & Kapurniotu, A. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.774893 · Cited by 62 · see citing works
Mo, Y., Brahmachari, S., Lei, J., Gilead, S., Tang, Y., Gazit, E., & Wei, G. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00166 · Cited by 62 · see citing works
Initiation of assembly of tau(273-284) and its ΔK280 mutant: an experimental and computational study
Larini, L., Gessel, M. M., LaPointe, N. E., Do, T. D., Bowers, M. T., Feinstein, S. C., & Shea, J. (2013) · Physical Chemistry Chemical Physics · doi:10.1039/c3cp00063j · Cited by 61 · see citing works
Self-citationNFGAIL Amyloid Oligomers: The Onset of Beta-Sheet Formation and the Mechanism for Fibril Formation
Hoffmann, W., Folmert, K., Moschner, J., Huang, X., von Berlepsch, H., Koksch, B., Bowers, M. T., von Helden, G., & Pagel, K. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b09510 · Cited by 60 · see citing works
Self-citationInteraction of amylin species with transition metals and membranes
Alghrably, M., Czaban, I., Jaremko, Ł., & Jaremko, M. (2018) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2018.11.004 · Cited by 58 · see citing works
Secondary Structure of Rat and Human Amylin across Force Fields
Hoffmann, K. Q., McGovern, M., Chiu, C., & Pablo, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134091 · Cited by 59 · see citing works
Sun, Y., Käkinen, A., Xing, Y., Pilkington, E. H., Davis, T. P., Ke, P. C., & Ding, F. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.11.021 · Cited by 59 · see citing works
The role of copper( ii ) in the aggregation of human amylin
Sinopoli, A., Magrì, A. L., Milardi, D., Pappalardo, M., Pucci, P., Flagiello, A., Titman, J. J., Nicoletti, V. G., Caruso, G., Pappalardo, G., et al. (2014) · Metallomics · doi:10.1039/c4mt00130c · Cited by 58 · see citing works
Young, L. M., Mahood, R. A., Saunders, J. C., Tu, L., Raleigh, D. P., Radford, S. E., & Ashcroft, A. E. (2015) · The Analyst · doi:10.1039/c5an00865d · Cited by 57 · see citing works
Cyclic Ion Mobility–Collision Activation Experiments Elucidate Protein Behavior in the Gas Phase
Eldrid, C., Ben-Younis, A., Ujma, J., Britt, H. M., Cragnolini, T., Kalfas, S., Cooper-Shepherd, D. A., Tomczyk, N., Giles, K., Morris, M., et al. (2021) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.1c00018 · Cited by 54 · see citing works
Conformational dynamics of α-synuclein: insights from mass spectrometry
Phillips, A. S., Gomes, A. F., Kalapothakis, J. M. D., Gillam, J., Gasparavicius, J., Gozzo, F. C., Kunath, T., MacPhee, C. E., & Barran, P. E. (2015) · The Analyst · doi:10.1039/c4an02306d · Cited by 56 · see citing works
Resveratrol interferes with the aggregation of membrane-bound human-IAPP: A molecular dynamics study
Lolicato, F., Raudino, A., Milardi, D., & Rosa, C. L. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.01.047 · Cited by 55 · see citing works
Effect of Proline Mutations on the Monomer Conformations of Amylin
Chiu, C., Singh, S., & Pablo, J. (2013) · Biophysical Journal · doi:10.1016/j.bpj.2013.07.029 · Cited by 54 · see citing works
Yan, L.-M., Velkova, A., Tatarek-Nossol, M., Rammes, G., Sibaev, A., Andreetto, E., Kracklauer, M., Bakou, M., Malideli, E., Göke, B., et al. (2013) · Angewandte Chemie · doi:10.1002/anie.201302840 · Cited by 55 · see citing works
Li, H., Ha, E., Donaldson, R. P., Jeremic, A., & Vertes, A. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b02217 · Cited by 45 · see citing works
α-helix to β-hairpin transition of human amylin monomer.
Singh, S., Chiu, C.-C., Reddy, A. S., & de Pablo, J. D. (2013) · Journal of Chemical Physics · doi:10.1063/1.4798460 · Cited by 48 · see citing works
Nguyen, P. T., Zottig, X., Sebastiao, M., & Bourgault, S. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00209 · Cited by 51 · see citing works
Zhang, M., Ren, B., Liu, Y., Liang, G., Sun, Y. P., Xu, L., & Zheng, J. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00160 · Cited by 50 · see citing works
Molecular Tweezers Inhibit Islet Amyloid Polypeptide Assembly and Toxicity by a New Mechanism
Lopes, D. H. J., Attar, A., Nair, G., Hayden, E. Y., Du, Z., McDaniel, K., Dutt, S., Bandmann, H., Bravo‐Rodriguez, K., Mittal, S., et al. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00146 · Cited by 48 · see citing works
Miller, C. M., Zerze, G. H., & Mittal, J. (2013) · The Journal of Physical Chemistry B · doi:10.1021/jp409755y · Cited by 48 · see citing works
Wineman‐Fisher, V., Atsmon‐Raz, Y., & Miller, Y. (2014) · Biomacromolecules · doi:10.1021/bm501326y · Cited by 47 · see citing works
β-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor
Mirecka, E. A., Feuerstein, S., Gremer, L., Schroeder, G. F., Stoldt, M., Willbold, D., & Hoyer, W. (2016) · Scientific Reports · doi:10.1038/srep33474 · Cited by 47 · see citing works
Lee, S. J. C., Choi, T. S., Lee, J. W., Lee, H. J., Mun, D., Akashi, S., Lee, S., Lim, M. H., & Kim, H. I. (2016) · Chemical Science · doi:10.1039/c6sc00153j · Cited by 46 · see citing works
Bellia, F., & Grasso, G. (2014) · Journal of Mass Spectrometry · doi:10.1002/jms.3338 · Cited by 45 · see citing works
Maj, M., Lomont, J. P., Rich, K. L., Alperstein, A. M., & Zanni, M. T. (2017) · Chemical Science · doi:10.1039/c7sc03789a · Cited by 45 · see citing works
Press‐Sandler, O., & Miller, Y. (2018) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2018.03.014 · Cited by 45 · see citing works
Novel insights into protein misfolding diseases revealed by ion mobility‐mass spectrometry
Williams, D. M., & Pukala, T. L. (2013) · Mass Spectrometry Reviews · doi:10.1002/mas.21358 · Cited by 43 · see citing works
Molecular simulation aspects of amyloid peptides at membrane interface
Liu, Y., Ren, B., Zhang, Y., Sun, Y. P., Chang, Y., Liang, G., Xu, L., & Zheng, J. (2018) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2018.02.004 · Cited by 43 · see citing works
France, A. P., Migas, L. G., Sinclair, E., Bellina, B., & Barran, P. E. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.9b05130 · Cited by 43 · see citing works
Understanding co-polymerization in amyloid formation by direct observation of mixed oligomers
Young, L. M., Tu, L., Raleigh, D. P., Ashcroft, A. E., & Radford, S. E. (2017) · Chemical Science · doi:10.1039/c7sc00620a · Cited by 41 · see citing works
Influence of fullerenol on hIAPP aggregation: amyloid inhibition and mechanistic aspects
Bai, C., Lin, D., Mo, Y., Lei, J., Sun, Y., Xie, L., Yang, X., & Wei, G. (2019) · Physical Chemistry Chemical Physics · doi:10.1039/c8cp07501h · Cited by 42 · see citing works
Mechanistic Insights into the Co-Aggregation of Aβ and hIAPP: An All-Atom Molecular Dynamic Study
Li, X., Lao, Z., Zou, Y. F., Dong, X., Li, L., & Wei, G. (2021) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.0c11132 · Cited by 42 · see citing works
Moore, S. J., Sonar, K., Bharadwaj, P., Deplazes, E., & Mancera, R. L. (2018) · Molecules · doi:10.3390/molecules23092142 · Cited by 41 · see citing works
Hoffmann, W., von Helden, G., & Pagel, K. (2017) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2017.03.002 · Cited by 40 · see citing works
Bai, C., Lao, Z., Chen, Y., Tang, Y., & Wei, G. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2020.00051 · Cited by 40 · see citing works
A Membrane‐Bound Antiparallel Dimer of Rat Islet Amyloid Polypeptide
Nath, A., Miranker, A. D., & Rhoades, E. R. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201102887 · Cited by 39 · see citing works
Moran, S. D., Decatur, S. M., & Zanni, M. T. (2012) · Journal of the American Chemical Society · doi:10.1021/ja307898g · Cited by 39 · see citing works
Dong, X., Qiao, Q., Qian, Z., & Wei, G. (2018) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2018.03.006 · Cited by 39 · see citing works
Introduction and Fundamentals of Human Islet Amyloid Polypeptide Inhibitors
Tang, Y., Zhang, D., Zhang, Y., Liu, Y., Gong, X., Chang, Y., Ren, B., & Zheng, J. (2020) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c01234 · Cited by 39 · see citing works
Sitkiewicz, E., Kłoniecki, M., Poznański, J. T., Bal, W., & Dadlez, M. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.05.015 · Cited by 38 · see citing works
Zhang, M., Hu, R., Liang, G., Chang, Y., Sun, Y. P., Peng, Z., & Zheng, J. (2014) · The Journal of Physical Chemistry B · doi:10.1021/jp5022246 · Cited by 37 · see citing works
Identification of Key Interactions in the Initial Self-Assembly of Amylin in a Membrane Environment
Christensen, M. H., Skeby, K. K., & Schiøtt, B. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00344 · Cited by 37 · see citing works
Jia, Y., Qian, Z., Zhang, Y., & Wei, G. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14036241 · Cited by 35 · see citing works
Zheng, X., Gessel, M. M., Wisniewski, M. L., Viswanathan, K., Wright, D. L., Bahr, B. A., & Bowers, M. T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.c111.328575 · Cited by 35 · see citing works
Self-citationOligomer Formation of Toxic and Functional Amyloid Peptides Studied with Atomistic Simulations
Carballo‐Pacheco, M., Ismail, A. E., & Strodel, B. (2015) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5b04822 · Cited by 35 · see citing works
Protein Glycation by Glyoxal Promotes Amyloid Formation by Islet Amyloid Polypeptide
Hsu, Y.-H., Chen, Y., Wu, M., & Tu, L. (2019) · Biophysical Journal · doi:10.1016/j.bpj.2019.05.013 · Cited by 35 · see citing works
Wang, H., Ridgway, Z. M., Cao, P., Ruzsicska, B. P., & Raleigh, D. P. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00567 · Cited by 35 · see citing works
Kirk, S. R., Liu, F. C., Cropley, T. C., Carlock, H. R., & Bleiholder, C. (2019) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-019-02200-y · Cited by 33 · see citing works
Symmetry-breaking transitions in the early steps of protein self-assembly
Rosa, C. L., Condorelli, M., Compagnini, G., Lolicato, F., Milardi, D., Do, T. N., Karttunen, M., Pannuzzo, M., Ramamoorthy, A., Fraternali, F., et al. (2020) · European Biophysics Journal · doi:10.1007/s00249-020-01424-1 · Cited by 33 · see citing works
Saini, R. K., Goyal, D., & Goyal, B. (2020) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.0c00416 · Cited by 33 · see citing works
Tu, L., Serrano, A. L., Zanni, M. T., & Raleigh, D. P. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2013.12.052 · Cited by 33 · see citing works
Ilitchev, A. I., Giammona, M. J., Do, T. D., Wong, A. G., Buratto, S. K., Shea, J., Raleigh, D. P., & Bowers, M. T. (2016) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-016-1347-7 · Cited by 33 · see citing works
Self-citationSingle-Molecular Heteroamyloidosis of Human Islet Amyloid Polypeptide
Käkinen, A., Xing, Y., Arachchi, N. D. H., Javed, I., Feng, L., Faridi, A., Douek, A. M., Sun, Y., Kaslin, J., Davis, T. P., et al. (2019) · Nano Letters · doi:10.1021/acs.nanolett.9b02771 · Cited by 32 · see citing works
Zhang, C., Samad, M., Yu, H., Chakroun, N., Hilton, D., & Dalby, P. A. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b00186 · Cited by 32 · see citing works
Zhang, J., Tan, J., Pei, R., & Ye, S. (2020) · Langmuir · doi:10.1021/acs.langmuir.9b03623 · Cited by 31 · see citing works
Saghir, A. E., Farrugia, G., & Vassallo, N. (2020) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2020.105010 · Cited by 30 · see citing works
Montané, J., Pablo, S., Castaño, C., Rodríguez‐Comas, J., Cadavez, L., Obach, M., Visa, M., Alcarraz‐Vizán, G., Sánchez-Martínez, M., Nonell‐Canals, A., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201700236r · Cited by 30 · see citing works
Chakraborty, S., Chatterjee, B., & Basu, S. (2012) · Biophysical Chemistry · doi:10.1016/j.bpc.2012.05.003 · Cited by 29 · see citing works
Fu, L., Wang, Z., Batista, V. S., & Yan, E. C. Y. (2015) · Journal of Diabetes Research · doi:10.1155/2016/7293063 · Cited by 29 · see citing works
- Authors
- Dupuis, N. F., Wu, C., Shea, J.-E., & Bowers, M. T.
- Affiliations
- University of California, Santa Barbara (US)
- Corresponding author
- Bowers, Michael T.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-04-25
- Volume
- 133
- Issue
- 19
- Pages
- 7240-7243
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC3093713
- OpenAlex
- W2061876586
- Cited by
- 216
- References
- 31
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 11 · 2020: 17 · 2019: 18 · 2018: 18 · 2017: 20 · 2016: 12 · 2015: 25 · 2014: 14 · 2013: 23 · 2012: 14
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P01AG027818)
- National Institute of General Medical Sciences (GM078114, R01GM078114)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- human islet amyloid polypeptide, type 2 diabetes, beta-cell death, all-atom molecular dynamics, N-methylation, protein self-interaction
- MeSH terms
- Animals, Humans, Models, Molecular, Surface Properties, Protein Structure, Secondary, Rats, Islet Amyloid Polypeptide
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
