Journal of Biosciences

, Volume 37, Issue 1, pp 13–17 | Cite as

What history tells us XXVII.

A new life for allostery
  • Michel Morange


The number of articles published on allostery has rapidly increased in recent years. Since the 1960s, the word ‘allostery’ has always had different meanings. On the one hand, allostery simply describes the conformational changes of proteins (and other macromolecules) following the binding of ligands. On the other hand, allostery may explicitly refer to the theory proposed by Jacques Monod, Jeffries Wyman and Jean-Pierre Changeux in 1965 – also known as the MWC model, or model of the concerted transition (Monod et al.1965). In this model, the allosteric change in conformation of proteins is not directly induced by the interaction of the proteins with their effectors, but results from the displacement of equilibrium between conformational states.

It is the latter vision of allostery that is flourishing at present, but with three significant extensions: the number of structural states is no longer limited to two but to an ensemble; allostery is not characteristic just of...


Allostery energy landscape molecular dynamics NMR 



I am indebted to David Marsh for his critical reading of the manuscript, and to Professor Michèle Reboud for my renewed interest in enzymology.


  1. Benkovic SJ, Hammes GG and Hammes-Schiffer S 2008 Free-energy landscape of enzyme catalysis. Biochemistry 47 3317–3321PubMedCrossRefGoogle Scholar
  2. Boehr DD, McElheny D, Dyson, HJ and Wright PE 2006 The dynamic energy landscape of dihydrofolate reductase catalysis. Science 313 1638–1642PubMedCrossRefGoogle Scholar
  3. Buc H 2006 Interactions between Jacques Monod and Jeffries Wyman (or the burdens of co-authorship); in Allosteric proteins – 40 years with Monod-Wyman-Changeux – Rendiconti di scienze fisiche e naturali Serie IX 17 (2) (Roma: Bardi)Google Scholar
  4. Changeux J-P 2003 A Ph.D. with Jacques Monod: Prehistory of allosteric proteins; in Origins of molecular biology: a tribute to Jacques Monod (ed) A Ullmann (Washington: ASM Press) pp 229–242Google Scholar
  5. Changeux J-P and Edelstein SJ 2005 Allosteric mechanisms of signal transduction. Science 308 1424–1428PubMedCrossRefGoogle Scholar
  6. Chouard T 2011 Breaking the protein rules. Nature 471 151–153PubMedCrossRefGoogle Scholar
  7. Creager ANH and Gaudillière J-P 1996 Meanings in search of experiments or vice-versa: The invention of allosteric regulation in Paris and Berkeley (1959-1967). Hist. Stud. Phys. Biol. Sci. 27 1–89CrossRefGoogle Scholar
  8. Cui O and Karplus M 2008 Allostery and cooperativity revisited. Protein Sci. 17 1295–1307Google Scholar
  9. del Sol A, Tsai CJ, Ma B and Nussinov R 2009 The origin of allosteric functional modulation: multiple pre-existing pathways. Structure 17 1042–1050PubMedCrossRefGoogle Scholar
  10. Eldar A and Elowitz MB 2010 Functional roles for noise in genetic circuits. Nature 467 167–173PubMedCrossRefGoogle Scholar
  11. Goodey NM and Benkovic SJ 2008 Allosteric regulation and catalysis emerge via a common route. Nat. Chem. Biol. 4 474–482PubMedCrossRefGoogle Scholar
  12. Gunasekaran K, Ma B and Nussinov R 2004 Is allostery an intrinsic property of all dynamic proteins? Proteins 57 433–443PubMedCrossRefGoogle Scholar
  13. Henzler-Wildman K and Kern D 2007 Dynamic personalities of proteins. Nature 450 964–972PubMedCrossRefGoogle Scholar
  14. Hilvert D 2000 Critical analysis of antibody catalysis. Annu. Rev. Biochem. 69 751–793PubMedCrossRefGoogle Scholar
  15. Kamiya D, Banno S, Sasai N, Ohgushi M , Inomata H, et al. 2011 Intrinsic transition of embryonic stem-cell differentiation into neural progenitors. Nature 470 503–509PubMedCrossRefGoogle Scholar
  16. Koshland DE Jr. 1958 Application of a theory of enzyme specificity to protein synthesis. Proc. Natl. Acad. Sci. USA 44 98–104Google Scholar
  17. Koshland DE, Nemethy G and Filmer D 1966 Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5 365–385PubMedCrossRefGoogle Scholar
  18. Kupiec JJ 2009 The origin of individuals (Singapore: World Scientific Publishing Company)CrossRefGoogle Scholar
  19. Lee J, Natarajan M, Nashine V C, Socolich M, Vo T, et al. 2008 Surface sites for engineering allosteric control in proteins. Science 322 438–442PubMedCrossRefGoogle Scholar
  20. Monod J and Jacob F 1961 General conclusions: Teleonomic mechanisms in cellular metabolism, growth, and differentiation. Cold Spring Harbor Symp. Quant. Biol. 26 389–401Google Scholar
  21. Monod J, Changeux J-P and Jacob F 1963 Allosteric proteins and cellular control systems. J. Mol. Biol. 6 306–329PubMedCrossRefGoogle Scholar
  22. Monod J, Wyman J and Changeux J-P 1965 On the nature of allosteric transition: A plausible model. J. Mol. Biol. 12 88–118PubMedCrossRefGoogle Scholar
  23. Nikolova EN, Kim E, Wise AA, O’Brien PJ, Andricioael I and Al-Hashimi HM 2011 Transient Hoogsteen base pairs in canonical duplex DNA. Nature 470 498–502PubMedCrossRefGoogle Scholar
  24. Oyama S, Griffiths P E and Gray R D (eds) 2001 Cycles of contingency: Developmental systems and evolution (Cambridge: The MIT Press)Google Scholar
  25. Palmer AG III and Massi F 2006 Characterization of the dynamics of biomacromolecules using rotating-frame spin relaxation NMR spectroscopy. Chem. Rev. 106 1700–1719PubMedCrossRefGoogle Scholar
  26. Shaw DE, Maragakis P, Lindorff-Larsen K, Plana S, Dror RO, et al. 2010 Atomic-level characterization of the structural dynamics of proteins. Science 330 341–346PubMedCrossRefGoogle Scholar
  27. Silva DA, Bowman GR, Sosa-Peinado A and Huang X 2011 A role for both conformational selection and induced fit in ligand binding by the LAO protein. PLOS Comput. Biol. 7 e1002054Google Scholar
  28. Tzeng S-R and Kalodimos CG 2009 Dynamic activation of an allosteric regulatory protein. Nature 462 368–372PubMedCrossRefGoogle Scholar
  29. Ullmann A 2003 Being around; in Origins of molecular biology: a tribute to Jacques Monod (ed) A Ullmann (Washington: ASM Press) pp 199–205Google Scholar
  30. Umbarger HE 1956 Evidence for a negative-feedback mechanism in the biosynthesis of isoleucine. Science 123 848Google Scholar
  31. Uversky VN 2002 Natively unfolded proteins: A point where biology waits for physics. Protein Sci. 11 739–756Google Scholar
  32. West-Eberhard MJ 2003 Developmental plasticity and evolution (Oxford: Oxford University Press)Google Scholar
  33. Winkler WC and Dann III CE 2006 RNA allostery glimpsed. Nat.e Struct. Mol. Boil. 13 569–571Google Scholar
  34. Wyman J 2003 Recollections of Jacques Monod; in Origins of molecular biology: a tribute to Jacques Monod (ed) A Ullmann (Washington: ASM Press) pp 263–267Google Scholar
  35. Yang S, Blachowicz L, Makowski L and Roux B 2010 Multidomain assembled states of Hck tyrosine kinase in solution. Proc. Natl. Acad. Sci. USA 107 15757–15762Google Scholar
  36. Yudkin J 1938 Enzyme variation in micro-organisms. Biol. Rev. 13 93–106CrossRefGoogle Scholar
  37. Zhuravlev PI and Papolan GA 2010 Protein functional landscapes, dynamics, allostery: a tortuous path towards a universal theoretical framework. Q. Rev. Biophys. 43 295–332PubMedCrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2012

Authors and Affiliations

  1. 1.Centre Cavaillès, CIRPHLES USR 3308, Ecole normale supérieureParis Cedex 05France

Personalised recommendations