Abstract
We review the idea that allosteric interactions can be transmitted not by structural switching but by the more subtle route of modulation of the amplitude of thermally-activated global dynamical modes in allosteric proteins. The effect is naturally addressed and explored through coarse-grained models of protein dynamics, but can be linked to atomistic models of substrate binding at the fine scale, and to themodynamic free energies at the macroscopic scale. A remarkable specificity at the residue level emerges: allosteric proteins possess a set of ‘control sites’ whose modification by single-point mutation may alter allosteric free-energies non-perturbatively.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Motlagh HN, Wrabl JO, Li J, Hilser VJ (2014) The ensemble nature of allostery. Nature 508:331–339. doi:10.1038/nature13001
Monod J, Wyman J, Changeux JP (1965) On the nature of allosteric transitions—a plausible model. J Mol Biol 12:88–118
Koshland DE Jr, Nemethy G, Filmer D (1966) Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5:365–385
Cooper A, Dryden DT (1984) Allostery without conformational change. A plausible model. Eur Biophys J 11:103–109
Hawkins RJ, McLeish TC (2004) Coarse-grained model of entropic allostery. Phys Rev Lett 93:098104
Hawkins RJ, McLeish TCB (2006) Coupling of global and local vibrational modes in dynamic allostery of proteins. Biophys J 91:2055–2062
Hawkins RJ, McLeish TCB (2006) Dynamic allostery of protein alpha helical coiled-coils. J R Soc Interface 3:125–138
Tzeng SR, Kalodimos CG (2009) Dynamic activation of an allosteric regulatory protein. Nature 462:368–372. doi:10.1038/nature08560
Tzeng SR, Kalodimos CG (2012) Protein activity regulation by conformational entropy. Nature 488:236–240. doi:10.1038/nature11271
Rodgers TL et al (2013) Modulation of global low-frequency motions underlies allosteric regulation: demonstration in CRP/FNR family transcription factors. PLoS Biol 11, e1001651. doi:10.1371/journal.pbio.1001651
Manley G, Rivalta I, Loria JP (2013) Solution NMR and computational methods for understanding protein allostery. J Phys Chem B 117:3063–3073. doi:10.1021/jp312576v
Wand AJ (2013) The dark energy of proteins comes to light: conformational entropy and its role in protein function revealed by NMR relaxation. Curr Opin Struct Biol 23:75–81. doi:10.1016/j.sbi.2012.11.005
Bahar I, Atilgan AR, Demirel MC, Erman B (1998) Vibrational dynamics of folded proteins: significance of slow and fast motions in relation to function and stability. Phys Rev Lett 80:2733–2736
McLeish TC, Rodgers TL, Wilson MR (2013) Allostery without conformation change: modelling protein dynamics at multiple scales. Phys Biol 10:056004. doi:10.1088/1478-3975/10/5/056004
Hilser VJ, Wrabl JO, Motlagh HN (2012) Structural and energetic basis of allostery. Annu Rev Biophys 41:585–609. doi:10.1146/annurev-biophys-050511-102319
Liu T, Whitten ST, Hilser VJ (2007) Functional residues serve a dominant role in mediating the cooperativity of the protein ensemble. Proc Natl Acad Sci U S A 104:4347–4352
Motlagh HN, Hilser VJ (2012) Agonism/antagonism switching in allosteric ensembles. Proc Natl Acad Sci U S A 109:4134–4139
Reynolds KA, McLaughlin RN, Ranganathan R (2011) Hot spots for allosteric regulation on protein surfaces. Cell 147:1564–1575. doi:10.1016/j.cell.2011.10.049
Zhuravleva A, Clerico EM, Gierasch LM (2012) An interdomain energetic tug-of-war creates the allosterically active state in Hsp70 Molecular chaperones. Cell 151:1296–1307. doi:10.1016/j.cell.2012.11.002
Zhuravleva A, Gierasch LM (2011) Allosteric signal transmission in the nucleotide-binding domain of 70-kDa heat shock protein (Hsp70) molecular chaperones. Proc Natl Acad Sci U S A 108:6987–6992. doi:10.1073/pnas.1014448108
Brooks B, Karplus M (1983) Harmonic dynamics of proteins: normal modes and fluctuations in bovine pancreatic trypsin inhibitor. Proc Natl Acad Sci U S A 80:6571–6575
Go N, Noguti T, Nishikawa T (1983) Dynamics of a small globular protein in terms of low-frequency vibrational modes. Proc Natl Acad Sci U S A 80:3696–3700
Tirion MM (1996) Large amplitude elastic motions in proteins from a single-parameter, atomic analysis. Phys Rev Lett 77:1905–1908
Delarue M, Sanejouand YH (2002) Simplified normal mode analysis of conformational transitions in DNA-dependent polymerases: the elastic network model. J Mol Biol 320:1011–1024
Valadie H, Lacapcre JJ, Sanejouand YH, Etchebest C (2003) Dynamical properties of the MscL of Escherichia coli: a normal mode analysis. J Mol Biol 332:657–674
Popovych N, Sun S, Ebright RH, Kalodimos CG (2006) Dynamically driven protein allostery. Nat Struct Mol Biol 13:831–838
Gorke B, Stulke J (2008) Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6:613–624. doi:10.1038/nrmicro1932
Rodgers TL, Burnell D, Townsend PD, Pohl E, Cann MJ, Wilson MR, McLeish TC (2013) ΔΔPT: a comprehensive toolbox for the analysis of protein motion. BMC Bioinf 14:183. doi:10.1186/1471-2105-14-183
Brown A (2009) Analysis of cooperativity by isothermal titration calorimetry. Int J Mol Sci 10:3457–3477. doi:10.3390/ijms10083457
Durand P, Trinquier G, Sanejouand YH (1994) New approach for determining low-frequency normal-modes in macromolecules. Biopolymers 34:759–771
Toncrova H, McLeish TCB (2010) Substrate-modulated thermal fluctuations affect long-range allosteric signaling in protein homodimers: exemplified in CAP. Biophys J 98:2317–2326
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this paper
Cite this paper
Townsend, P.D., Rodgers, T.L., Pohl, E., Wilson, M.R., Cann, M.J., McLeish, T.C.B. (2015). Multi-scale Approaches to Dynamical Transmission of Protein Allostery. In: Olivares-Quiroz, L., Guzmán-López, O., Jardón-Valadez, H. (eds) Physical Biology of Proteins and Peptides. Springer, Cham. https://doi.org/10.1007/978-3-319-21687-4_8
Download citation
DOI: https://doi.org/10.1007/978-3-319-21687-4_8
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-21686-7
Online ISBN: 978-3-319-21687-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)