Principles of Allosteric Interactions in Cell Signaling
Open accessAbstract
Linking cell signaling events to the fundamental physicochemical basis of the conformational behavior of single molecules and ultimately to cellular function is a key challenge facing the life sciences. Here we outline the emerging principles of allosteric interactions in cell signaling, with emphasis on the following points. (1) Allosteric efficacy is not a function of the chemical composition of the allosteric pocket but reflects the extent of the population shift between the inactive and active states. That is, the allosteric effect is determined by the extent of preferred binding, not by the overall binding affinity. (2) Coupling between the allosteric and active sites does not decide the allosteric effect; however, it does define the propagation pathways, the allosteric binding sites, and key on-path residues. (3) Atoms of allosteric effectors can act as “driver” or “anchor” and create attractive “pulling” or repulsive “pushing” interactions. Deciphering, quantifying, and integrating the multiple co-occurring events present daunting challenges to our scientific community.
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Allostery and signaling are properties of populations.
“Allostery and signaling are properties of populations.”
From AlphaFold, Artificial Intelligence (AI), and Allostery (2022) · cites this paper as [119]
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1 retracted
Geetha, N., Mihaly, J., Stockenhuber, A., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.221903 · Cited by 32 · see citing works
RetractedCell Signaling by Receptor Tyrosine Kinases
Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929 · see citing works
Mechanism of Activation of the RAF-ERK Signaling Pathway by Oncogenic Mutations of B-RAF
Wan, P., Garnett, M. J., Roe, S. M., Lee, S., Niculescu‐Duvaz, D., Good, V. M., Cancer Genome Project, Jones, C. M., Marshall, C. J., Springer, C. J., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00215-6 · Cited by 2,800 · see citing works
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer
Roberts, P. J., & Der, C. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210422 · Cited by 2,788 · see citing works
From Levinthal to pathways to funnels
Dill, K. A., & Chan, H. S. (1997) · Nature Structural & Molecular Biology · doi:10.1038/nsb0197-10 · Cited by 2,293 · see citing works
The role of dynamic conformational ensembles in biomolecular recognition
Boehr, D. D., Nussinov, R., & Wright, P. E. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.232 · Cited by 2,008 · see citing works
Self-citationCOT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460 · see citing works
Evolutionarily Conserved Pathways of Energetic Connectivity in Protein Families
Lockless, S. W., & Ranganathan, R. (1999) · Science · doi:10.1126/science.286.5438.295 · Cited by 1,288 · see citing works
Wolynes, P., Onuchic, J., & Thirumalai, D. (1995) · Science · doi:10.1126/science.7886447 · Cited by 1,080 · see citing works
Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions
Liu, W., Chun, E., Thompson, A. A., Chubukov, P., Xu, F., Katritch, V., Han, G. W., Roth, C., Heitman, L. H., IJzerman, A. P., et al. (2012) · Science · doi:10.1126/science.1219218 · Cited by 948 · see citing works
Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways
Schulman, B. A., & Harper, J. W. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2673 · Cited by 944 · see citing works
Is allostery an intrinsic property of all dynamic proteins?
Gunasekaran, K., Ma, B., & Nussinov, R. (2004) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20232 · Cited by 882 · see citing works
Self-citationCsermely, P., Palotai, R., & Nussinov, R. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.009 · Cited by 821 · see citing works
Self-citationAllostery in Disease and in Drug Discovery
Nussinov, R., & Tsai, C. (2013) · Cell · doi:10.1016/j.cell.2013.03.034 · Cited by 764 · see citing works
Self-citationProtein Sectors: Evolutionary Units of Three-Dimensional Structure
Halabi, N. M., Rivoire, O., Leibler, S., & Ranganathan, R. (2009) · Cell · doi:10.1016/j.cell.2009.07.038 · Cited by 697 · see citing works
Allostery and cooperativity revisited
Cui, Q., & Karplus, M. (2008) · Protein Science · doi:10.1110/ps.03259908 · Cited by 680 · see citing works
DNA binding site sequence directs glucocorticoid receptor structure and activity
Meijsing, S. H., Pufall, M. A., So, A. Y., Bates, D. L., Chen, L., & Yamamoto, K. R. (2009) · Science · doi:10.1126/science.1164265 · Cited by 673 · see citing works
Allosteric regulation and catalysis emerge via a common route
Goodey, N. M., & Benkovic, S. J. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.98 · Cited by 667 · see citing works
Folding funnels, binding funnels, and protein function
Tsai, C., Kumar, S., Ma, B., & Nussinov, R. (1999) · Protein Science · doi:10.1110/ps.8.6.1181 · Cited by 648 · see citing works
Self-citationFolding and binding cascades: Dynamic landscapes and population shifts
Kumar, S., Ma, B., Tsai, C., Sinha, N., & Nussinov, R. (2000) · Protein Science · doi:10.1110/ps.9.1.10 · Cited by 595 · see citing works
Self-citationFolding funnels and binding mechanisms
Ma, B., Kumar, S., Tsai, C.-J., & Nussinov, R. (1999) · Protein Engineering, Design and Selection · doi:10.1093/protein/12.9.713 · Cited by 594 · see citing works
Self-citationMolecular Mechanism of β-Arrestin-Biased Agonism at Seven-Transmembrane Receptors
Reiter, É., Ahn, S., Shukla, A. K., & Lefkowitz, R. J. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105800 · Cited by 582 · see citing works
Hidden alternative structures of proline isomerase essential for catalysis
Fraser, J. S., Clarkson, M. W., Degnan, S. C., Erion, R., Kern, D., & Alber, T. (2009) · Nature · doi:10.1038/nature08615 · Cited by 509 · see citing works
The two-state model of receptor activation
Leff, P. (1995) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)88989-0 · Cited by 500 · see citing works
Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate
Bertelsen, E., Chang, L., Gestwicki, J., & Zuiderweg, E. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0903503106 · Cited by 461 · see citing works
Allostery: Absence of a change in shape does not imply that allostery is not at play
Tsai, C.-J., del Sol, A., & Nussinov, R. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.02.034 · Cited by 453 · see citing works
Self-citationMultiple diverse ligands binding at a single protein site: A matter of pre‐existing populations
Ma, B., Shatsky, M., Wolfson, H. J., & Nussinov, R. (2002) · Protein Science · doi:10.1110/ps.21302 · Cited by 420 · see citing works
Self-citationStructure and dynamics of the ATP-bound open conformation of Hsp70 chaperones.
Kityk, R., Kopp, J., Sinning, I., & Mayer, M. P. (2012) · Molecules and Cells · doi:10.1016/j.molcel.2012.09.023 · Cited by 412 · see citing works
Mechanism of the nuclear receptor molecular switch
Nagy, L. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.04.006 · Cited by 406 · see citing works
Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins
Hilser, V. J., & Thompson, E. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700329104 · Cited by 406 · see citing works
A Unified View of “How Allostery Works”
Tsai, C.-J., & Nussinov, R. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003394 · Cited by 401 · see citing works
Self-citationThe Origin of Allosteric Functional Modulation: Multiple Pre-existing Pathways
del Sol, A., Tsai, C., Ma, B., & Nussinov, R. (2009) · Structure · doi:10.1016/j.str.2009.06.008 · Cited by 365 · see citing works
Self-citationFolding and binding cascades: Shifts in energy landscapes
Tsai, C.-J., Ma, B., & Nussinov, R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.9970 · Cited by 365 · see citing works
Self-citationHot Spots for Allosteric Regulation on Protein Surfaces
Reynolds, K. A., McLaughlin, R. N., & Ranganathan, R. (2011) · Cell · doi:10.1016/j.cell.2011.10.049 · Cited by 350 · see citing works
Surface Sites for Engineering Allosteric Control in Proteins
Lee, J., Natarajan, M., Nashine, V. C., Socolich, M., Vo, T., Russ, W. P., Benkovic, S. J., & Ranganathan, R. (2008) · Science · doi:10.1126/science.1159052 · Cited by 345 · see citing works
Tsai, C., del Sol, A., & Nussinov, R. (2009) · Molecular BioSystems · doi:10.1039/b819720b · Cited by 324 · see citing works
Self-citationAllosteric Supramolecular Triple-Layer Catalysts
Yoon, H. J., Kuwabara, J., Kim, J., & Mirkin, C. A. (2010) · Science · doi:10.1126/science.1193928 · Cited by 321 · see citing works
Leitner, D. M. (2008) · Annual Review of Physical Chemistry · doi:10.1146/annurev.physchem.59.032607.093606 · Cited by 311 · see citing works
Conformational switch of syntaxin-1 controls synaptic vesicle fusion
Gerber, S. H., Rah, J.-C., Min, S.-W., Liu, X., de Wit, H., Dulubova, I., Meyer, A. C., Rizo, J., Arancillo, M., Hammer, R. E., et al. (2008) · Science · doi:10.1126/science.1163174 · Cited by 294 · see citing works
Inhibitor hijacking of Akt activation
Okuzumi, T., Fiedler, D., Zhang, C., Gray, D. C., Aizenstein, B., Hoffman, R., & Shokat, K. M. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.183 · Cited by 294 · see citing works
Kim, S., Broströmer, E., Xing, D., Jin, J., Chong, S., Ge, H., Wang, S. S., Gu, C., Yang, L., Gao, Y. Q., et al. (2013) · Science · doi:10.1126/science.1229223 · Cited by 293 · see citing works
Korzhnev, D. M., & Kay, L. E. (2008) · Accounts of Chemical Research · doi:10.1021/ar700189y · Cited by 266 · see citing works
Energy Landscapes as a Tool to Integrate GPCR Structure, Dynamics, and Function
Deupí, X., & Kobilka, B. K. (2010) · Physiology · doi:10.1152/physiol.00002.2010 · Cited by 265 · see citing works
Protein dynamics and allostery: an NMR view
Tzeng, S., & Kalodimos, C. G. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.10.007 · Cited by 256 · see citing works
Zhuravleva, A., Clerico, E. M., & Gierasch, L. (2012) · Cell · doi:10.1016/j.cell.2012.11.002 · Cited by 253 · see citing works
The role of conformational entropy in molecular recognition by calmodulin
Marlow, M. S., Dogan, J., Frederick, K. K., Valentine, K. G., & Wand, A. J. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.347 · Cited by 251 · see citing works
Exploring the folding landscape of a structured RNA
Russell, R., Zhuang, X., Babcock, H. P., Millett, I. S., Doniach, S., Chu, S., & Herschlag, D. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.221593598 · Cited by 235 · see citing works
Mapping allostery through the covariance analysis of NMR chemical shifts
Selvaratnam, R., Chowdhury, S., VanSchouwen, B., & Melacini, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017311108 · Cited by 228 · see citing works
Intramolecular Signaling Pathways Revealed by Modeling Anisotropic Thermal Diffusion
Ota, N., & Agard, D. A. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.05.043 · Cited by 227 · see citing works
Basis for a ubiquitin-like protein thioester switch toggling E1–E2 affinity
Huang, D. T. C., Hunt, H. W., Zhuang, M., Ohi, M. D., Holton, J. M., & Schulman, B. A. (2007) · Nature · doi:10.1038/nature05490 · Cited by 227 · see citing works
Dynamic Allostery: Linkers Are Not Merely Flexible
Ma, B., Tsai, C.-J., Haliloğlu, T., & Nussinov, R. (2011) · Structure · doi:10.1016/j.str.2011.06.002 · Cited by 222 · see citing works
Self-citationp53-family proteins and their regulators: hubs and spokes in tumor suppression
Collavin, L., Lunardi, A., & Sal, G. D. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.35 · Cited by 219 · see citing works
The role of distant mutations and allosteric regulation on LovD active site dynamics
Jiménez‐Osés, G., Osuna, S., Gao, X., Sawaya, M. R., Gilson, L., Collier, S. J., Huisman, G. W., Yeates, T. O., Tang, Y., & Houk, K. N. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1503 · Cited by 211 · see citing works
Allosteric post-translational modification codes
Nussinov, R., Tsai, C.-J., Xin, F., & Radivojac, P. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.07.001 · Cited by 211 · see citing works
Self-citationStructured disorder and conformational selection
Tsai, C., Ma, B., Sham, Y. Y., Kumar, S., & Nussinov, R. (2001) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.1107 · Cited by 202 · see citing works
Self-citationAllostery and population shift in drug discovery
Kar, G., Keskin, Ö., Gürsoy, A., & Nussinov, R. (2010) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2010.09.002 · Cited by 190 · see citing works
Self-citationGerek, Z. N., & Ozkan, S. B. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002154 · Cited by 189 · see citing works
Hall, D. A. (2000) · Molecular Pharmacology · doi:10.1124/mol.58.6.1412 · Cited by 185 · see citing works
Molecular Recognition by Induced Fit: How Fit is the Concept?
Bosshard, H. R. (2001) · Physiology · doi:10.1152/physiologyonline.2001.16.4.171 · Cited by 184 · see citing works
Activity-enhancing mutations in an E3 ubiquitin ligase identified by high-throughput mutagenesis
Starita, L. M., Pruneda, J. N., Lo, R. S., Fowler, D. M., Kim, H. J., Hiatt, J. B., Shendure, J., Brzovic, P. S., Fields, S., & Klevit, R. E. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303309110 · Cited by 183 · see citing works
The Underappreciated Role of Allostery in the Cellular Network
Nussinov, R., Tsai, C., & Ma, B. (2013) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-083012-130257 · Cited by 174 · see citing works
Self-citationAn ATP-Site On-Off Switch That Restricts Phosphatase Accessibility of Akt
Lin, K., Lin, J. M., Wu, W., Ballard, J. A., Lee, B. B., Gloor, S. L., Vigers, G. P. A., Morales, T. H., Friedman, L. S., Skelton, N. J., et al. (2012) · Science Signaling · doi:10.1126/scisignal.2002618 · Cited by 174 · see citing works
Wand, A. J. (2012) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2012.11.005 · Cited by 173 · see citing works
Dynamic protein–DNA recognition: beyond what can be seen
Fuxreiter, M., Simon, I., & Bondos, S. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.04.006 · Cited by 167 · see citing works
Das, R., Mariano, J. M., Tsai, Y. C., Kalathur, R., Kostova, Z., Li, J., Tarasov, S. G., McFeeters, R. L., Altieri, A. S., Ji, X., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.05.010 · Cited by 160 · see citing works
Mechanisms of transcription factor selectivity
Pan, Y., Tsai, C., Ma, B., & Nussinov, R. (2010) · Trends in Genetics · doi:10.1016/j.tig.2009.12.003 · Cited by 158 · see citing works
Self-citationPorchetta, A., Vallée‐Bélisle, A., Plaxco, K. W., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja310585e · Cited by 156 · see citing works
Signal Amplification by Allosteric Catalysis
Zhu, L., & Anslyn, E. V. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200501476 · Cited by 151 · see citing works
p53 activates transcription by directing structural shifts in Mediator
Meyer, K. D., Lin, S., Bernecky, C., Gao, Y., & Taatjes, D. J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1816 · Cited by 144 · see citing works
Allo-network drugs: harnessing allostery in cellular networks
Nussinov, R., Tsai, C., & Csermely, P. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.08.004 · Cited by 143 · see citing works
Self-citationIκB kinase regulation of the TPL‐2/ERK MAPK pathway
Gantke, T., Sriskantharajah, S., Sadowski, M. I., & Ley, S. C. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01104.x · Cited by 143 · see citing works
How Potassium Affects the Activity of the Molecular Chaperone Hsc70
Wilbanks, S. M., & McKay, D. B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.5.2251 · Cited by 138 · see citing works
Zhuravlev, P. I., & Papoian, G. A. (2010) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583510000119 · Cited by 138 · see citing works
Microscopic Insights into the NMR Relaxation-Based Protein Conformational Entropy Meter
Kasinath, V., Sharp, K. A., & Wand, A. J. (2013) · Journal of the American Chemical Society · doi:10.1021/ja405200u · Cited by 133 · see citing works
Multiple conformational selection and induced fit events take place in allosteric propagation
Nussinov, R., Ma, B., & Tsai, C. (2013) · Biophysical Chemistry · doi:10.1016/j.bpc.2013.10.002 · Cited by 130 · see citing works
Self-citationNRF2, cancer and calorie restriction
Martín‐Montalvo, A., Villalba, J. M., Navas, P., & de Cabo, R. (2010) · Oncogene · doi:10.1038/onc.2010.492 · Cited by 128 · see citing works
‘7TM Receptor Allostery: Putting Numbers to Shapeshifting Proteins
Kenakin, T. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.06.007 · Cited by 126 · see citing works
Allosterically Tunable, DNA-Based Switches Triggered by Heavy Metals
Porchetta, A., Vallée‐Bélisle, A., Plaxco, K. W., & Ricci, F. (2013) · Journal of the American Chemical Society · doi:10.1021/ja404653q · Cited by 120 · see citing works
Unraveling structural mechanisms of allosteric drug action
Nussinov, R., & Tsai, C.-J. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.03.006 · Cited by 119 · see citing works
Self-citationEstrogen Response Elements Function as Allosteric Modulators of Estrogen Receptor Conformation
Wood, J. R., Greene, G. L., & Nardulli, A. M. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.4.1927 · Cited by 110 · see citing works
Transient Non-native Hydrogen Bonds Promote Activation of a Signaling Protein
Gardino, A. K., Villali, J., Kivenson, A., Lei, M., Liu, C. F., Steindel, P. A., Eisenmesser, E. Z., Labeikovsky, W., Wolf‐Watz, M., Clarkson, M. W., et al. (2009) · Cell · doi:10.1016/j.cell.2009.11.022 · Cited by 107 · see citing works
Gupta, M., Hendrickson, A. E. W., Yun, S. S., Han, J., Schneider, P. A., Koh, B. D., Stenson, M. J., Wellik, L. E., Shing, J. C., Peterson, K. L., et al. (2011) · Blood · doi:10.1182/blood-2011-04-346601 · Cited by 103 · see citing works
The role of DNA response elements as allosteric modulators of steroid receptor function
Geserick, C., Meyer, H., & Haendler, B. (2005) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2005.03.007 · Cited by 102 · see citing works
Pump‐probe molecular dynamics as a tool for studying protein motion and long range coupling
Sharp, K. A., & Skinner, J. J. (2006) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21146 · Cited by 98 · see citing works
Liu, J., & Nussinov, R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707401105 · Cited by 95 · see citing works
Self-citationLipid binding by the Unique and SH3 domains of c-Src suggests a new regulatory mechanism
Pérez, Y., Maffei, M., Igea, A., Amata, I., Gairí, M., Nebreda, Á. R., Bernadó, P., & Pons, M. (2013) · Scientific Reports · doi:10.1038/srep01295 · Cited by 90 · see citing works
Regulation of the catalytic activity of the EGF receptor
Endres, N., Engel, K., Das, R., Kovács, E., & Kuriyan, J. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.07.007 · Cited by 90 · see citing works
Directed Evolution and Structural Characterization of a Simvastatin Synthase
Gao, X., Xie, X., Pashkov, I., et al. (2009) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.09.017 · Cited by 87 · see citing works
Resistance of Akt kinases to dephosphorylation through ATP-dependent conformational plasticity
Chan, T. O., Zhang, J., Rodeck, U., Pascal, J. M., Armen, R. S., Spring, M., Dumitru, C. D., Myers, V. D., Li, X., Cheung, J. Y., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109879108 · Cited by 86 · see citing works
Dixit, A., & Verkhivker, G. M. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002179 · Cited by 81 · see citing works
NMR insights into protein allostery
Manley, G. A., & Loria, J. P. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2011.10.023 · Cited by 78 · see citing works
Frameworks for Understanding Long-Range Intra-Protein Communication
Whitley, M. J., & Lee, A. R. (2009) · Current Protein and Peptide Science · doi:10.2174/138920309787847563 · Cited by 76 · see citing works
Allosteric inhibition of individual enzyme molecules trapped in lipid vesicles
Piwoński, H., Goomanovsky, M., Bensimon, D., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116670109 · Cited by 75 · see citing works
Functional anatomy of an allosteric protein
Purohit, P. G., Gupta, S., Jadey, S. V., & Auerbach, A. L. (2013) · Nature Communications · doi:10.1038/ncomms3984 · Cited by 71 · see citing works
Two Classes of Androgen Receptor Elements Mediate Cooperativity through Allosteric Interactions
Reid, K. J., Hendy, S. C., Saito, J., Sørensen, P. D., & Nelson, C. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009170200 · Cited by 70 · see citing works
Functional Dynamics of PDZ Binding Domains: A Normal-Mode Analysis
Rios, P. D. L., Cecconi, F., Pretre, A., et al. (2005) · Biophysical Journal · doi:10.1529/biophysj.104.055004 · Cited by 69 · see citing works
Clore, G. M. (2008) · Molecular BioSystems · doi:10.1039/b810232e · Cited by 69 · see citing works
Gerek, Z. N., Keskin, Ö., & Ozkan, S. B. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22492 · Cited by 66 · see citing works
Allosteric Communication across the Native and Mutated KIT Receptor Tyrosine Kinase
Laine, É., Auclair, C., & Tchertanov, L. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002661 · Cited by 65 · see citing works
The allosteric communication pathways in KIX domain of CBP
Palazzesi, F., Barducci, A., Tollinger, M., & Parrinello, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313548110 · Cited by 62 · see citing works
Allosteric Conformational Barcodes Direct Signaling in the Cell
Nussinov, R., Ma, B., Tsai, C.-J., & Csermely, P. (2013) · Structure · doi:10.1016/j.str.2013.06.002 · Cited by 55 · see citing works
Self-citationLiu, J., & Nussinov, R. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000527 · Cited by 55 · see citing works
Self-citationControlling Proteins Through Molecular Springs
Zocchi, G. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.050708.133637 · Cited by 55 · see citing works
Ziarek, J. J., Getschman, A. E., Butler, S. J., Taleski, D., Stephens, B. S., Kufareva, I., Handel, T. M., Payne, R. J., & Volkman, B. F. (2013) · ACS Chemical Biology · doi:10.1021/cb400274z · Cited by 53 · see citing works
Flexible Cullins in Cullin-RING E3 Ligases Allosterically Regulate Ubiquitination
Liu, J., & Nussinov, R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.277236 · Cited by 52 · see citing works
Self-citationThe structural basis for cancer treatment decisions
Nussinov, R., Jang, H., & Tsai, C. (2014) · Oncotarget · doi:10.18632/oncotarget.2439 · Cited by 51 · see citing works
Self-citationThe spatial structure of cell signaling systems
Nussinov, R. (2013) · Physical Biology · doi:10.1088/1478-3975/10/4/045004 · Cited by 49 · see citing works
Self-citationAtomistic Kinetic Model for Population Shift and Allostery in Biomolecules
Long, D., & Brüschweiler, R. (2011) · Journal of the American Chemical Society · doi:10.1021/ja208813t · Cited by 48 · see citing works
Specific phosphorylation and activation of ERK1c by MEK1b: a unique route in the ERK cascadePreprint
Shaul, Y. D., Gibor, G., Plotnikov, A. N., & Seger, R. (2009) · Genes & Development · doi:10.1101/gad.523909 · Cited by 47 · see citing works
Simon, A. J., Vallée‐Bélisle, A., Ricci, F., et al. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201403777 · Cited by 47 · see citing works
PSCDB: a database for protein structural change upon ligand binding
Amemiya, T., Koike, R., Kidera, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr966 · Cited by 47 · see citing works
Allosteric Effects Govern Nuclear Receptor Action: DNA Appears as a Player
Gronemeyer, H., & Bourguet, W. (2009) · Science Signaling · doi:10.1126/scisignal.273pe34 · Cited by 46 · see citing works
Evolving a robust signal transduction pathway from weak cross‐talk
Siryaporn, A., Perchuk, B. S., Laub, M. T., & Goulian, M. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.105 · Cited by 46 · see citing works
Identification of an Allosteric Signaling Network within Tec Family Kinases
Joseph, R. E., Xie, Q., & Andreotti, A. H. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.08.035 · Cited by 43 · see citing works
Korkmaz, E. N., Nussinov, R., & Haliloǧlu, T. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002420 · Cited by 40 · see citing works
Self-citationBlackmore, N. J., Reichau, S., Jiao, W., Hutton, R. D., Baker, E. N., Jameson, G. B., & Parker, E. J. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.12.019 · Cited by 39 · see citing works
Liu, J., & Nussinov, R. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.01.022 · Cited by 37 · see citing works
Self-citationThe role of allostery in the ubiquitin–proteasome system
Liu, J., & Nussinov, R. (2012) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2012.742856 · Cited by 35 · see citing works
Self-citationHansen, D. F., Vallurupalli, P., & Kay, L. E. (2009) · Journal of the American Chemical Society · doi:10.1021/ja903897e · Cited by 35 · see citing works
Gene-specific transcription activation via long-range allosteric shape-shifting
Tsai, C., & Nussinov, R. (2011) · Biochemical Journal · doi:10.1042/bj20110972 · Cited by 34 · see citing works
Self-citationFree Energy Diagrams for Protein Function
Nussinov, R., & Tsai, C. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.12.015 · Cited by 31 · see citing works
Self-citationHormone Binding and Co-regulator Binding to the Glucocorticoid Receptor are Allosterically Coupled
Pfaff, S. J., & Fletterick, R. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.108118 · Cited by 29 · see citing works
Identifying Key Residues for Protein Allostery through Rigid Residue Scan
Kalescky, R. J. B., Liu, J., & Tao, P. (2014) · The Journal of Physical Chemistry A · doi:10.1021/jp5083455 · Cited by 29 · see citing works
Self-citationDNA-binding specificity and in vivo targets of Caenorhabditis elegans nuclear factor I
Whittle, C. M., Lazakovitch, E., Gronostajski, R. M., & Lieb, J. D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812894106 · Cited by 28 · see citing works
Liu, J., & Nussinov, R. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.05.021 · Cited by 26 · see citing works
Self-citationMolecular Basis for the pH Dependent Structural Transition of Nitrophorin 4
Marti, M. A., Estrin, D. A., & Roitberg, A. E. (2009) · The Journal of Physical Chemistry B · doi:10.1021/jp808055e · Cited by 19 · see citing works
Nussinov, R. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01793.x · Cited by 16 · see citing works
Self-citationFas, B. A., Tutar, Y., & Haliloǧlu, T. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003141 · Cited by 12 · see citing works
During Transitions Proteins Make Fleeting Bonds
Boehr, D. D. (2009) · Cell · doi:10.1016/j.cell.2009.11.031 · Cited by 12 · see citing works
Kumar, G., & Frantom, P. A. (2014) · Biochemistry · doi:10.1021/bi500702u · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Palmer A. G.; Kroenke C. D.; Loria J. P. Nucl. Magn. Reson. Biol. Macromol., B 2001, 339, 204.
- Liu J.; Nussinov R. Crit. Rev. Biochem. Mol. Biol. 2013, 48, 89. 23234564 PMC3609921
Cited by
Sorted by citations
Wei, G., Xi, W., Nussinov, R., & Ma, B. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00562 · Cited by 436 · see citing works
Self-citationAllostery: An Overview of Its History, Concepts, Methods, and Applications
Liu, J., & Nussinov, R. (2016) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1004966 · Cited by 281 · see citing works
Self-citationDrugging Ras GTPase: a comprehensive mechanistic and signaling structural view
Lu, S., Jang, H., Gu, S., Zhang, J., & Nussinov, R. (2016) · Chemical Society Reviews · doi:10.1039/c5cs00911a · Cited by 188 · see citing works
Self-citationThe Role of Conformational Dynamics and Allostery in Modulating Protein Evolution
Campitelli, P., Modi, T., Kumar, S., & Ozkan, S. B. (2020) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-052118-115517 · Cited by 190 · see citing works
AlphaFold, Artificial Intelligence (AI), and Allostery
Nussinov, R., Zhang, M., Liu, Y., & Jang, H. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.2c04346 · Cited by 190 · see citing works
Self-citationASD v3.0: unraveling allosteric regulation with structural mechanisms and biological networks
Shen, Q., Wang, G., Li, S., Liu, X., Lu, S., Chen, Z., Song, K., Yan, J., Geng, L., Huang, Z., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv902 · Cited by 122 · see citing works
Ni, D., Lu, S., & Zhang, J. (2019) · Medicinal Research Reviews · doi:10.1002/med.21585 · Cited by 116 · see citing works
- Authors
- Nussinov, R., Tsai, C.-J., & Liu, J.
- Affiliations
- Tel Aviv University (IL)
- Frederick National Laboratory for Cancer Research (US)
- Southern Methodist University (US)
- Corresponding author
- Nussinov, Ruth
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-12-04
- Volume
- 136
- Issue
- 51
- Pages
- 17692-17701
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC4291754
- OpenAlex
- W2055560422
- Cited by
- 154
- References
- 130
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 12 · 2023: 17 · 2022: 14 · 2021: 12 · 2020: 16 · 2019: 18 · 2018: 8 · 2017: 13 · 2016: 16 · 2015: 9
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of the American Chemical Society (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (HHSN261200800001E)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- allosteric interactions, signal transduction, allosteric effectors, allosteric pocket, allosteric site, allosteric communication, protein conformational dynamics
- MeSH terms
- Allosteric Regulation, Models, Biological, Signal Transduction, Catalytic Domain
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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.
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