Lipid-Dependent Alternating Access Mechanism of a Bacterial Multidrug ABC Exporter
Open accessAbstract
By undergoing conformational changes, active membrane transporters alternate between an inward-facing (IF) and an outward-facing (OF) state to transport their substrates across cellular membrane. The conformational landscape of membrane transporters, however, could be influenced by their environment, and the dependence of the alternating access mechanism on the lipid composition has not been understood at the molecular level. We have performed an extensive set of microsecond-level all-atom molecular dynamics (MD) simulations on bacterial ATP binding cassette (ABC) exporter Sav1866 in six different phosphocholine (PC) and phosphoethanolamine (PE) lipid membrane environments. This study mainly focuses on the energetically downhill OF-to-IF conformational transition of Sav1866 upon the ATP hydrolysis. We observe that the transporter undergoes large-scale conformational changes in the PE environment, particularly in the POPE lipids, resulting in an IF-occluded conformation, a transition that does not occur when the transporter is embedded in any of the PC lipid bilayers. We propose that the PE lipids facilitate the closing of the protein on the periplasmic side due to their highly polar headgroups that mediate the interaction of the two transmembrane (TM) bundles by a network of lipid-lipid and lipid-protein hydrogen bonds. POPE lipids in particular facilitate the closure of periplasmic gate by promoting a hinge formation in TM helices and an interbundle salt bridge formation. This study explains how the alternating access mechanism and the flippase activity in ABC exporters could be lipid-dependent.
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 lipid environment has been experimentally shown to bias the conformational equilibria of membrane proteins.
“which has been experimentally shown to bias the conformational equilibria of membrane proteins (Martens et al., 2018; Muller et al., 2019; Immadisetty et al., 2019).”
From Sampling alternative conformational states of transporters and receptors with AlphaFold2 (2022) · cites this paper as Immadisetty et al., 2019
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
VMD: visual molecular dynamics
Humphrey, W., Dalke, A., & Schulten, K. (1996) · Journal of Molecular Graphics · doi:10.1016/0263-7855(96)00018-5 · Cited by 66,952 · see citing works
Comparison of simple potential functions for simulating liquid water
Jorgensen, W. L., Chandrasekhar, J., Madura, J., Impey, R., & Klein, M. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445869 · Cited by 38,335 · see citing works
Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems
Darden, T., York, D., & Pedersen, L. (1993) · The Journal of Chemical Physics · doi:10.1063/1.464397 · Cited by 29,588 · see citing works
Scalable molecular dynamics with NAMD
Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R. D., Kalé, L., & Schulten, K. (2005) · Journal of Computational Chemistry · doi:10.1002/jcc.20289 · Cited by 16,914 · see citing works
Constant pressure molecular dynamics algorithms
Martyna, G. J., Tobias, D. J., & Klein, M. L. (1994) · The Journal of Chemical Physics · doi:10.1063/1.467468 · Cited by 5,845 · see citing works
Multidrug resistance in cancer: role of ATP–dependent transporters
Gottesman, M. M., Fojo, T., & Bates, S. E. (2002) · Nature Reviews Cancer · doi:10.1038/nrc706 · Cited by 5,536 · see citing works
Best, R. B., Zhu, X., Shim, J., Lopes, P. E. M., Mittal, J., Feig, M., & MacKerell, A. D. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300400x · Cited by 4,472 · see citing works
Update of the CHARMM all-atom additive force field for lipids: Validation on six lipid types
Klauda, J. B., Venable, R., Freites, J. A., O'Connor, J. W., Tobias, D., Mondragon-Ramirez, C., Vorobyov, I., MacKerell, A. D., & Pastor, R. (2010) · Journal of Physical Chemistry B · doi:10.1021/jp101759q · Cited by 4,369 · see citing works
Constant pressure molecular dynamics simulation: The Langevin piston method
Feller, S., Zhang, Y., Pastor, R., & Brooks, B. (1995) · The Journal of Chemical Physics · doi:10.1063/1.470648 · Cited by 4,267 · see citing works
Lee, J.-M., Cheng, X., Swails, J. M., Yeom, M. S., Eastman, P., Lemkul, J. A., Wei, S., Buckner, J., Jeong, J. C., Qi, Y., et al. (2015) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.5b00935 · Cited by 4,238 · see citing works
Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding
Aller, S. G., Yu, J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P. M., Trinh, Y. T., Zhang, Q., Urbatsch, I. L., et al. (2009) · Science · doi:10.1126/science.1168750 · Cited by 1,929 · see citing works
Structure, Function, and Evolution of Bacterial ATP-Binding Cassette Systems
Davidson, A. L., Dassa, E., Orelle, C., & Chen, J. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00031-07 · Cited by 1,422 · see citing works
Simple Allosteric Model for Membrane Pumps
Jardetzky, O. (1966) · Nature · doi:10.1038/211969a0 · Cited by 1,293 · see citing works
Structure of a bacterial multidrug ABC transporter
Dawson, R. J. P., & Locher, K. P. (2006) · Nature · doi:10.1038/nature05155 · Cited by 1,280 · see citing works
How lipids affect the activities of integral membrane proteins
LEE, A. G. J. (2004) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2004.05.012 · Cited by 1,195 · see citing works
Automated Builder and Database of Protein/Membrane Complexes for Molecular Dynamics Simulations
Jo, S., Kim, T., & Im, W. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000880 · Cited by 1,186 · see citing works
ProDy : Protein Dynamics Inferred from Theory and Experiments
Bakan, A., Meireles, L., & Bahar, İ. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr168 · Cited by 1,113 · see citing works
The E. coli BtuCD Structure: A Framework for ABC Transporter Architecture and Mechanism
Locher, K. P., Lee, A. T., & Rees, D. C. (2002) · Science · doi:10.1126/science.1071142 · Cited by 1,025 · see citing works
Multiple molecular mechanisms for multidrug resistance transporters
Higgins, C. F. (2007) · Nature · doi:10.1038/nature05630 · Cited by 863 · see citing works
Flexibility in the ABC transporter MsbA: Alternating access with a twist
Ward, A. B., Reyes, C. L., Yu, J., Roth, C., & Chang, G. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709388104 · Cited by 774 · see citing works
The ATP switch model for ABC transporters
Higgins, C. F., & Linton, K. J. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb836 · Cited by 752 · see citing works
Sarkadi, B., Homolya, L., Szakács, G., & Váradi, A. (2006) · Physiological Reviews · doi:10.1152/physrev.00037.2005 · Cited by 726 · see citing works
Structure and mechanism of ABC transporter proteins
Hollenstein, K., Dawson, R. J. P., & Locher, K. P. (2007) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2007.07.003 · Cited by 672 · see citing works
ABC transporters: physiology, structure and mechanism – an overview
Higgins, C. F. (2001) · Research in Microbiology · doi:10.1016/s0923-2508(01)01193-7 · Cited by 643 · see citing works
The ABC transporter structure and mechanism: perspectives on recent research
Jones, P. M., & George, A. M. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3336-9 · Cited by 578 · see citing works
The molecular basis of multidrug resistance in cancer: The early years of P‐glycoprotein research
Gottesman, M. M., & Ling, V. (2006) · FEBS Letters · doi:10.1016/j.febslet.2005.12.060 · Cited by 558 · see citing works
The P-glycoprotein multidrug transporter
Sharom, F. J. (2011) · Essays in Biochemistry · doi:10.1042/bse0500161 · Cited by 508 · see citing works
Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans
Jin, M. S., Oldham, M. L., Zhang, Q., & Chen, J. (2012) · Nature · doi:10.1038/nature11448 · Cited by 467 · see citing works
Dawson, R. J. P., & Locher, K. P. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.01.073 · Cited by 408 · see citing works
ABC proteins : from bacteria to man
Holland, I. B., Cole, S. P. C., Kuchler, K., & Higgins, C. F. (2003) · Medical Entomology and Zoology · Cited by 361 · see citing works
GridMAT‐MD: A grid‐based membrane analysis tool for use with molecular dynamics
Allen, W. J., Lemkul, J. A., & Bevan, D. R. (2008) · Journal of Computational Chemistry · doi:10.1002/jcc.21172 · Cited by 317 · see citing works
Role of ABC transporters in lipid transport and human disease
Tarling, E. J., Vallim, T. Q. D. A., & Edwards, P. A. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.01.006 · Cited by 301 · see citing works
ABC transporters in lipid transport
Borst, P., Zelcer, N., & van Helvoort, A. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(00)00053-6 · Cited by 301 · see citing works
MEMBPLUGIN: studying membrane complexity in VMD
Guixà-González, R., Rodríguez‐Espigares, I., Ramírez‐Anguita, J. M., Carrió, P., Martinez‐Seara, H., Toni Giorgino, A., & Selent, J. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu037 · Cited by 300 · see citing works
Sharom, F. J. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00041 · Cited by 283 · see citing works
Muller, M. P., Jiang, T., Sun, C., Lihan, M., Pant, S., Mahinthichaichan, P., Trifan, A., & Tajkhorshid, E. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00608 · Cited by 282 · see citing works
Structural insights into ABC transporter mechanism
Oldham, M. L., Davidson, A. L., & Chen, J. (2008) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2008.09.007 · Cited by 272 · see citing works
Ward, A. B., Szewczyk, P., Grimard, V., Lee, C., Martinez, L., Doshi, R., Caya, A., Villaluz, M., Pardon, E., Cregger, C., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309275110 · Cited by 257 · see citing works
Daleke, D. L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.r600035200 · Cited by 250 · see citing works
Energy transduction and alternating access of the mammalian ABC transporter P-glycoprotein
Verhalen, B., Dastvan, R., Thangapandian, S., Peskova, Y. B., Koteiche, H. A., Nakamoto, R. K., Tajkhorshid, E., & Mchaourab, H. S. (2017) · Nature · doi:10.1038/nature21414 · Cited by 249 · see citing works
Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation
Hohl, M., Briand, C., Grütter, M. G., & Seeger, M. A. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2267 · Cited by 245 · see citing works
Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states
Shintre, C. A., Pike, A. C. W., Li, Q., Kim, J.-I., Barr, A., Goubin, S., Shrestha, L., Yang, J., Berridge, G., Ross, J. E., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217042110 · Cited by 240 · see citing works
MsbA-dependent Translocation of Lipids across the Inner Membrane of Escherichia coli
Doerrler, W. T., Gibbons, H. S., & Raetz, C. R. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408106200 · Cited by 236 · see citing works
Lipids as a Target for Drugs Modulating Multidrug Resistance of Cancer Cells
Hendrich, A. B., & Michalak, K. (2003) · Current Drug Targets · doi:10.2174/1389450033347172 · Cited by 206 · see citing works
Mechanistic picture for conformational transition of a membrane transporter at atomic resolution
Moradi, M., & Tajkhorshid, E. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313202110 · Cited by 159 · see citing works
Procko, E., O’Mara, M. L., Bennett, W. F., Tieleman, D. P., & Gaudet, R. (2009) · The FASEB Journal · doi:10.1096/fj.08-121855 · Cited by 158 · see citing works
Phospholipid Flippase Activity of the Reconstituted P-Glycoprotein Multidrug Transporter
Romsicki, Y., & Sharom, F. J. (2001) · Biochemistry · doi:10.1021/bi0024456 · Cited by 155 · see citing works
Ahn, J., Wong, J. T., & Molday, R. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000555200 · Cited by 130 · see citing works
On the Origin of Large Flexibility of P-glycoprotein in the Inward-facing State
Wen, P., 溫, 博., Verhalen, B., Wilkens, S., Mchaourab, H. S., & Tajkhorshid, E. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.450114 · Cited by 127 · see citing works
Large Sparse Sets of Linear Equations
H., A. S., & Reid, J. K. (1973) · Mathematics of Computation · doi:10.2307/2005268 · Cited by 126 · see citing works
A subset of annular lipids is linked to the flippase activity of an ABC transporter
Bechara, C., Noll, A., Morgner, N., Degiacomi, M. T., Tampé, R., & Robinson, C. V. (2015) · Nature Chemistry · doi:10.1038/nchem.2172 · Cited by 124 · see citing works
Mishra, S., Verhalen, B., Stein, R. A., Wen, P., Tajkhorshid, E., & Mchaourab, H. S. (2014) · eLife · doi:10.7554/elife.02740 · Cited by 124 · see citing works
Distinct Conformational Spectrum of Homologous Multidrug ABC Transporters
Moeller, A., Lee, S. C., Tao, H., Speir, J. A., Chang, G. A., Urbatsch, I. L., Potter, C. S., Carragher, B. O., & Zhang, Q. (2015) · Structure · doi:10.1016/j.str.2014.12.013 · Cited by 118 · see citing works
Moradi, M., Enkavi, G., & Tajkhorshid, E. (2015) · Nature Communications · doi:10.1038/ncomms9393 · Cited by 113 · see citing works
An ABC transporter with a secondary-active multidrug translocator domain
Venter, H., Shilling, R. A., Velamakanni, S., Balakrishnan, L., & van Veen, H. W. (2003) · Nature · doi:10.1038/nature02173 · Cited by 111 · see citing works
Zhang, W., Bogdanov, M. V., Pi, J., Pittard, A. J., & Dowhan, W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m309840200 · Cited by 110 · see citing works
Topology of polytopic membrane protein subdomains is dictated by membrane phospholipid composition
Wang, X., Bogdanov, M. V., & Dowhan, W. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf571 · Cited by 110 · see citing works
Phospholipids as Determinants of Membrane Protein Topology
Zhang, W., Campbell, H. A., King, S. C., & Dowhan, W. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504929200 · Cited by 107 · see citing works
Evolution of ABC transporters by gene duplication and their role in human disease
Moitra, K., & Dean, M. C. (2011) · Biological Chemistry · doi:10.1515/bc.2011.006 · Cited by 96 · see citing works
Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP
Noll, A., Thomas, C., Herbring, V., Zollmann, T., Barth, K., Mehdipour, A. R., Tomasiak, T. M., Brüchert, S., Joseph, B., Abele, R., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620009114 · Cited by 94 · see citing works
Structural basis for antibacterial peptide self‐immunity by the bacterial ABC transporter McjD
Bountra, K., Hagelueken, G., Choudhury, H. G., Corradi, V., Omari, K. E., Wagner, A., Mathavan, I., Zirah, S., Wahlgren, W. Y., Tieleman, D. P., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201797278 · Cited by 88 · see citing works
The extracellular gate shapes the energy profile of an ABC exporter
Hutter, C. A. J., Timachi, M. H., Hürlimann, L. M., Zimmermann, I., Egloff, P., Göddeke, H., Kucher, S., Štefanić, S., Karttunen, M., Schäfer, L. V., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09892-6 · Cited by 82 · see citing works
Moradi, M., & Tajkhorshid, E. (2014) · Journal of Chemical Theory and Computation · doi:10.1021/ct5002285 · Cited by 74 · see citing works
Asymmetric Switching in a Homodimeric ABC Transporter: A Simulation Study
Aittoniemi, J., de Wet, H., Ashcroft, F. M., & Sansom, M. S. P. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000762 · Cited by 72 · see citing works
Interactions between Phosphatidylethanolamine Headgroup and LmrP, a Multidrug Transporter
Hakizimana, P., Masureel, M., Gbaguidi, B., Ruysschaert, J., & Govaerts, C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708427200 · Cited by 72 · see citing works
Oliveira, A. S. F., Baptista, A. M., & Soares, C. M. (2011) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.23023 · Cited by 61 · see citing works
Weng, J., Fan, K., & Wang, W. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.056432 · Cited by 54 · see citing works
Atomistic Mechanism of Large-Scale Conformational Transition in a Heterodimeric ABC Exporter
Göddeke, H., Timachi, M. H., Hutter, C. A. J., Galazzo, L., Seeger, M. A., Karttunen, M., Bordignon, E., & Schäfer, L. V. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.7b12944 · Cited by 49 · see citing works
O’Mara, M. L., & Mark, A. E. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300254y · Cited by 48 · see citing works
Yahyavi, M., Falsafi-Zadeh, S., Karimi, Z., Kalatarian, G., & Galehdari, H. (2014) · Bioinformation · doi:10.6026/97320630010548 · Cited by 47 · see citing works
Dynamics and Structural Changes Induced by ATP Binding in SAV1866, a Bacterial ABC Exporter
Becker, J., Françoise Van Bambeke, A., Tulkens, P. M., & Prévost, M. (2010) · The Journal of Physical Chemistry B · doi:10.1021/jp1038392 · Cited by 46 · see citing works
Gustot, A., Smriti, S., Ruysschaert, J., Mchaourab, H. S., & Govaerts, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.079673 · Cited by 45 · see citing works
A 32x32x32, spatially distributed 3D FFT in four microseconds on Anton
Young, C., Bank, J. A., Dror, R. O., Grossman, J. P., Salmon, J. K., & Shaw, D. E. (2009) · International Conference for High Performance Computing, Networking, Storage and Analysis (SC) · doi:10.1145/1654059.1654083 · Cited by 41 · see citing works
Molecular Dynamics Simulations of the Bacterial ABC Transporter SAV1866 in the Closed Form
St‐Pierre, J., Bunker, A., Róg, T., Karttunen, M., & Mousseau, N. (2012) · The Journal of Physical Chemistry B · doi:10.1021/jp209126c · Cited by 39 · see citing works
Bao, H., Dalal, K., Wang, V., Rouiller, I., & Duong, F. (2013) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2013.03.024 · Cited by 36 · see citing works
Computational Dissection of Membrane Transport at a Microscopic Level
Jiang, T., Wen, P., Trebesch, N., Zhao, Z., Pant, S., Kapoor, K., Shekhar, M., & Tajkhorshid, E. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.09.001 · Cited by 29 · see citing works
Structural Characterization of Two Metastable ATP-Bound States of P-Glycoprotein
O’Mara, M. L., & Mark, A. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091916 · Cited by 27 · see citing works
Gu, R., Corradi, V., Singh, G., Choudhury, H. G., Beis, K., & Tieleman, D. P. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00753 · Cited by 25 · see citing works
Immadisetty, K., Hettige, J. J., & Moradi, M. (2016) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6b09733 · Cited by 24 · see citing works
Unidirectional Transport Mechanism in an ATP Dependent Exporter
Xu, Y., Seelig, A., & Bernèche, S. (2017) · ACS Central Science · doi:10.1021/acscentsci.7b00068 · Cited by 22 · see citing works
Effects of lipid environment on the conformational changes of an ABC importer
Rice, A. J., Alvarez, F. J. D., Davidson, A. L., & Pinkett, H. W. (2014) · Channels · doi:10.4161/chan.29294 · Cited by 18 · see citing works
A Review of Monoamine Transporter-Ligand Interactions
Immadisetty, K., & Madura, J. D. (2013) · Current Computer - Aided Drug Design · doi:10.2174/15734099113096660039 · Cited by 15 · see citing works
Harkey, T., Kumar, V. G., Hettige, J. J., Tabari, S. H., Immadisetty, K., & Moradi, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-51052-9 · Cited by 15 · see citing works
Effective Riemannian Diffusion Model for Conformational Dynamics of Biomolecular Systems
Fakharzadeh, A., & Moradi, M. (2016) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.6b02208 · Cited by 13 · see citing works
Furuta, T., Sato, Y., & Sakurai, M. (2016) · Biochemistry · doi:10.1021/acs.biochem.6b00947 · Cited by 13 · see citing works
The mammalian ABC transporter ABCA1 induces lipid-dependent drug sensitivity in yeast
Bocer, T., Zarubica, A., Roussel‐Queval, A., Flis, K., Trombik, T., Goffeau, A., Ułaszewski, S., & Chimini, G. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.07.005 · Cited by 11 · see citing works
An Effective Electric Dipole Model for Voltage-induced Gating Mechanism of Lysenin
Faouri, R. A., Krueger, E. E., Kumar, V. G., Fologea, D., Straub, D., Alismail, H., Alfaori, Q., Kight, A. D., Ray, J., Henry, R. L., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-47725-0 · Cited by 4 · see citing works
Flagged first, then by citations
1 of the 88 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Sampling alternative conformational states of transporters and receptors with AlphaFold2
del Alamo, D., Sala, D., Mchaourab, H. S., & Meiler, J. (2022) · eLife · doi:10.7554/elife.75751 · Cited by 511 · see citing works
“Moreover, AF2 does not directly account for the lipid environment, which has been experimentally shown to bias the conformational equilibria of membrane proteins ( Martens et al., 2018 ; Muller et al., 2019 ; Immadisetty et al., 2019 ).”
BackgroundPhospholipids and cholesterol: Inducers of cancer multidrug resistance and therapeutic targets
Kopecka, J., Trouillas, P., Gašparović, A. Č., Gazzano, E., Assaraf, Y. G., & Riganti, C. (2019) · Drug Resistance Updates · doi:10.1016/j.drup.2019.100670 · Cited by 296 · see citing works
Muller, M. P., Jiang, T., Sun, C., Lihan, M., Pant, S., Mahinthichaichan, P., Trifan, A., & Tajkhorshid, E. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00608 · Cited by 282 · see citing works
The extracellular gate shapes the energy profile of an ABC exporter
Hutter, C. A. J., Timachi, M. H., Hürlimann, L. M., Zimmermann, I., Egloff, P., Göddeke, H., Kucher, S., Štefanić, S., Karttunen, M., Schäfer, L. V., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09892-6 · Cited by 82 · see citing works
ATP-binding cassette (ABC) transporters: structures and roles in bacterial pathogenesis
How, S. S., Nathan, S., Lam, S. D., & Chieng, S. (2024) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2300641 · Cited by 59 · see citing works
Selective Nutrient Transport in Bacteria: Multicomponent Transporter Systems Reign Supreme
Davies, J. S., Currie, M. J., Wright, J. D., Newton-Vesty, M. C., North, R. A., Mace, P. D., Allison, J. R., & Dobson, R. C. J. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.699222 · Cited by 57 · see citing works
Rasouli, A., Yu, Q., Dehghani‐Ghahnaviyeh, S., Wen, P., Kowal, J., Locher, K. P., & Tajkhorshid, E. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2213437120 · Cited by 40 · see citing works
MLCV: Bridging Machine-Learning-Based Dimensionality Reduction and Free-Energy Calculation
Chen, H., Liu, H., Feng, H., Fu, H., Cai, W., Shao, X., & Chipot, C. J. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.1c01010 · Cited by 37 · see citing works
Capturing Substrate Translocation in an ABC Exporter at the Atomic Level
Göddeke, H., & Schäfer, L. V. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c05502 · Cited by 36 · see citing works
Principles of Alternating Access in LeuT-fold Transporters: Commonalities and Divergences
del Alamo, D., Meiler, J., & Mchaourab, H. S. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167746 · Cited by 33 · see citing works
Computational Dissection of Membrane Transport at a Microscopic Level
Jiang, T., Wen, P., Trebesch, N., Zhao, Z., Pant, S., Kapoor, K., Shekhar, M., & Tajkhorshid, E. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.09.001 · Cited by 29 · see citing works
Structural dynamics of ABC transporters: molecular simulation studies
Furuta, T. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200710 · Cited by 27 · see citing works
Tangella, L. P., Arooj, M., Deplazes, E., Gray, E. S., & Mancera, R. L. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.12.042 · Cited by 24 · see citing works
On the interplay between lipids and asymmetric dynamics of an NBS degenerate ABC transporter
Tóth, Á., Janaszkiewicz, A., Crespi, V., & Meo, F. D. (2023) · Communications Biology · doi:10.1038/s42003-023-04537-3 · Cited by 19 · see citing works
Badiee, S. A., Isu, U. H., Khodadadi, E., & Moradi, M. (2023) · Membranes · doi:10.3390/membranes13060568 · Cited by 19 · see citing works
Harkey, T., Kumar, V. G., Hettige, J. J., Tabari, S. H., Immadisetty, K., & Moradi, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-51052-9 · Cited by 15 · see citing works
The Important Role of Transporter Structures in Drug Disposition, Efficacy, and Toxicity
Fu, T., Zeng, S., Zheng, Q., & Zhu, F. (2023) · Drug Metabolism and Disposition · doi:10.1124/dmd.123.001275 · Cited by 13 · see citing works
Ardalan, A., Sowlati‐Hashjin, S., Uwumarenogie, S. O., Fish, M., Mitchell, J., Karttunen, M., Smith, M. D., & Jelokhani‐Niaraki, M. (2020) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.0c09422 · Cited by 13 · see citing works
Cholesterol metabolism: A strategy for overcoming drug resistance in tumors
Li, J., Guo, Y., Zhang, W., Xia, M. H., Liu, G., Sun, Y. P., Liu, C. X., & Zhong, J. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.116974 · Cited by 10 · see citing works
Modulation of P2X4 pore closure by magnesium, potassium, and ATP
Immadisetty, K., Alenciks, J., & Kekenes-Huskey, P. M. (2022) · Biophysical Journal · doi:10.1016/j.bpj.2022.02.038 · Cited by 9 · see citing works
Elucidating the molecular basis of spontaneous activation in an engineered mechanosensitive channel
Immadisetty, K., Polasa, A., Shelton, R., & Moradi, M. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.05.022 · Cited by 8 · see citing works
Pant, S., Dehghani‐Ghahnaviyeh, S., Trebesch, N., Rasouli, A., Chen, T., Kapoor, K., Wen, P., & Tajkhorshid, E. (2025) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5c00104 · Cited by 7 · see citing works
Tóth, Á., Crespi, V., Janaszkiewicz, A., & Meo, F. D. (2023) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13871 · Cited by 6 · see citing works
Immadisetty, K., & Moradi, M. (2021) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.1c03982 · Cited by 5 · see citing works
Polasa, A., Hettige, J. J., Immadisetty, K., & Moradi, M. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.954262 · Cited by 5 · see citing works
An Effective Electric Dipole Model for Voltage-induced Gating Mechanism of Lysenin
Faouri, R. A., Krueger, E. E., Kumar, V. G., Fologea, D., Straub, D., Alismail, H., Alfaori, Q., Kight, A. D., Ray, J., Henry, R. L., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-47725-0 · Cited by 4 · see citing works
Meshkin, H., & Zhu, F. (2021) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.1c00585 · Cited by 4 · see citing works
Computing Individual Area per Head Group Reveals Lipid Bilayer Dynamics
Greenfield, M. L., Martin, L. M., & Joodaki, F. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.2c04633 · Cited by 3 · see citing works
Polasa, A., Hettige, J. J., Immadisetty, K., & Moradi, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.28.493840 · Cited by 2 · see citing works
Benton, M., Furr, M., Kumar, V. G., Polasa, A., Gao, F., Heyes, C. D., Kumar, T. K. S., & Moradi, M. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c00319 · Cited by 2 · see citing works
Deciphering the Interdomain Coupling in a Gram-Negative Bacterial Membrane Insertase
Polasa, A., Badiee, S. A., & Moradi, M. (2024) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.4c02824 · Cited by 4 · see citing works
Experimental and Computational Evidence for Self-Assembly of Mitochondrial UCP2 in Lipid BilayersPreprint
Ardalan, A., Uwumarenogie, S. O., Fish, M., Sowlati‐Hashjin, S., Karttunen, M., Smith, M. D., & Jelokhani‐Niaraki, M. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/430835 · Cited by 2 · see citing works
Deciphering the Inter-domain Decoupling in the Gram-negative Bacterial Membrane InsertasePreprint
Polasa, A., Badiee, S. A., & Moradi, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.09.503346 · Cited by 2 · see citing works
Membrane organization | Lipid Transporters: Flippases, Floppases and Scramblases
Visintainer, D., & López‐Marqués, R. L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819460-7.00064-5 · Cited by 1 · see citing works
Lipid-dependent conformational dynamics of bacterial ATP-binding cassette transporter Sav1866Preprint
Badiee, S. A., Hettige, J. J., & Moradi, M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.18.590185
Dynamic framework for large-scale modeling of membranes and peripheral proteins
Sadeghi, M., & Rosenberger, D. (2024) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2024.03.018
Ghosh, K., Baid, H. V., Dasgupta, P., & Kanaujia, S. P. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.149605
Kinetic asymmetry drives directionality in an ATP-binding cassette transporterPreprint
Rudolph, M., Batebi, H., Pramod, M., Barth, K., Hirschberg, C., Tampé, R., Netz, R. R., & Joseph, B. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.11.751009
- Authors
- Immadisetty, K., Hettige, J., & Moradi, M.
- Affiliations
- University of Arkansas at Fayetteville (US)
- Corresponding author
- Moradi, Mahmoud
- Venue
- ACS Central Science
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-01-07
- Volume
- 5
- Issue
- 1
- Pages
- 43-56
- ISSN
- 2374-7943 (ISSN-L)
- 2374-7951
- PMC
- PMC6346382
- OpenAlex
- W2907088041
- Cited by
- 38
- References
- 88
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 1
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- ACS Central Science (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Arkansas
- Arkansas Biosciences Institute
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- Sav1866, ABC transporters, alternating access mechanism, lipid dependence, Pope, ATP hydrolysis, salt bridges
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
