Parallel dynamics and evolution: Protein conformational fluctuations and assembly reflect evolutionary changes in sequence and structure

Protein structure is dynamic: the intrinsic flexibility of polypeptides facilitates a range of conformational fluctuations, and individual protein chains can assemble into complexes. Proteins are also dynamic in evolution: significant variations in secondary, tertiary and quaternary structure can be observed among divergent members of a protein family. Recent work has highlighted intriguing similarities between these structural and evolutionary dynamics occurring at various levels. Here we review evidence showing how evolutionary changes in protein sequence and structure are often closely related to local protein flexibility and disorder, large‐scale motions and quaternary structure assembly. We suggest that these correspondences can be largely explained by neutral evolution, while deviations between structural and evolutionary dynamics can provide valuable functional insights. Finally, we address future prospects for the field and practical applications that arise from a deeper understanding of the intimate relationship between protein structure, dynamics, function and evolution.

[1]  J. C. Kendrew,et al.  Structure and function of haemoglobin: II. Some relations between polypeptide chain configuration and amino acid sequence , 1965 .

[2]  T. Ohta,et al.  On some principles governing molecular evolution. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[3]  C. Chothia.  The nature of the accessible and buried surfaces in proteins. , 1976, Journal of molecular biology.

[4]  S. Beychok,et al.  Probes of subunit assembly and reconstitution pathways in multisubunit proteins. , 1979, Annual review of biochemistry.

[5]  A. Lesk,et al.  How different amino acid sequences determine similar protein structures: the structure and evolutionary dynamics of the globins. , 1980, Journal of molecular biology.

[6]  C. Y. Huang,et al.  On the mechanism of activation of the ATP X Mg(II)-dependent phosphoprotein phosphatase by kinase FA. , 1984, The Journal of biological chemistry.

[7]  A. Lesk,et al.  The relation between the divergence of sequence and structure in proteins. , 1986, The EMBO journal.

[8]  M. Karplus,et al.  Multiple conformational states of proteins: a molecular dynamics analysis of myoglobin. , 1987, Science.

[9]  Cyrus Chothia,et al.  The accessible surface area and stability of oligomeric proteins , 1987, Nature.

[10]  P. Wolynes,et al.  The energy landscapes and motions of proteins. , 1991, Science.

[11]  John P. Overington,et al.  Environment‐specific amino acid substitution tables: Tertiary templates and prediction of protein folds , 1992, Protein science : a publication of the Protein Society.

[12]  C. Dobson,et al.  Structural determinants of protein dynamics: analysis of 15N NMR relaxation measurements for main-chain and side-chain nuclei of hen egg white lysozyme. , 1995, Biochemistry.

[13]  D Eisenberg,et al.  3D domain swapping: A mechanism for oligomer assembly , 1995, Protein science : a publication of the Protein Society.

[14]  F. Cohen,et al.  An evolutionary trace method defines binding surfaces common to protein families. , 1996, Journal of molecular biology.

[15]  P Argos,et al.  Correlation between side chain mobility and conformation in protein structures. , 1997, Protein engineering.

[16]  David C. Jones,et al.  Assessing the impact of secondary structure and solvent accessibility on protein evolution. , 1998, Genetics.

[17]  D. Eisenberg,et al.  Detecting protein function and protein-protein interactions from genome sequences. , 1999, Science.

[18]  Anton J. Enright,et al.  Protein interaction maps for complete genomes based on gene fusion events , 1999, Nature.

[19]  R. Ranganathan,et al.  Evolutionarily conserved pathways of energetic connectivity in protein families. , 1999, Science.

[20]  R. Jernigan,et al.  Proteins with similar architecture exhibit similar large-scale dynamic behavior. , 2000, Biophysical journal.

[21]  Y. Sanejouand,et al.  Conformational change of proteins arising from normal mode calculations. , 2001, Protein engineering.

[22]  C. Pál,et al.  Highly expressed genes in yeast evolve slowly. , 2001, Genetics.

[23]  Christopher J. Oldfield,et al.  Evolutionary Rate Heterogeneity in Proteins with Long Disordered Regions , 2002, Journal of Molecular Evolution.

[24]  M Karplus,et al.  Relation between sequence and structure of HIV-1 protease inhibitor complexes: a model system for the analysis of protein flexibility. , 2002, Journal of molecular biology.

[25]  B. Halle,et al.  Flexibility and packing in proteins , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Rafael Brüschweiler,et al.  Contact model for the prediction of NMR N-H order parameters in globular proteins. , 2002, Journal of the American Chemical Society.

[27]  L. Vitagliano,et al.  Subtle functional collective motions in pancreatic‐like ribonucleases: From ribonuclease A to angiogenin , 2003, Proteins.

[28]  J. Thornton,et al.  Structural characterisation and functional significance of transient protein-protein interactions. , 2003, Journal of molecular biology.

[29]  M. Sansom,et al.  Molecular dynamics simulations of a K+ channel blocker: Tc1 toxin from Tityus cambridgei , 2003, FEBS letters.

[30]  L. Kay,et al.  Correlation between 2H NMR side-chain order parameters and sequence conservation in globular proteins. , 2003, Journal of the American Chemical Society.

[31]  R. Nussinov,et al.  Protein–protein interactions: Structurally conserved residues distinguish between binding sites and exposed protein surfaces , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Andrew L. Lee,et al.  Ligand-dependent dynamics and intramolecular signaling in a PDZ domain. , 2004, Journal of molecular biology.

[33]  Paul Weakliem,et al.  Statistical coevolution analysis and molecular dynamics: identification of amino acid pairs essential for catalysis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Dan S. Tawfik,et al.  The 'evolvability' of promiscuous protein functions , 2005, Nature Genetics.

[35]  E. Jaffe.  Morpheeins--a new structural paradigm for allosteric regulation. , 2005, Trends in biochemical sciences.

[36]  I. Bahar,et al.  Structural changes involved in protein binding correlate with intrinsic motions of proteins in the unbound state. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[37]  D. Zerbino,et al.  An analysis of core deformations in protein superfamilies. , 2005, Biophysical journal.

[38]  P. Biggin,et al.  Comparative molecular dynamics—Similar folds and similar motions? , 2005, Proteins.

[39]  Jianpeng Ma,et al.  Usefulness and limitations of normal mode analysis in modeling dynamics of biomolecular complexes. , 2005, Structure.

[40]  A Pandini,et al.  Conservation and specialization in PAS domain dynamics. , 2005, Protein engineering, design & selection : PEDS.

[41]  J. Echave,et al.  Evolutionary Conservation of Protein Backbone Flexibility , 2006, Journal of Molecular Evolution.

[42]  C. Wilke,et al.  Why highly expressed proteins evolve slowly. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Julian Echave,et al.  Exploring the common dynamics of homologous proteins. Application to the globin family. , 2005, Biophysical journal.

[44]  Christopher T. Saunders,et al.  Recapitulation of protein family divergence using flexible backbone protein design. , 2005, Journal of molecular biology.

[45]  M. DePristo,et al.  Relation between native ensembles and experimental structures of proteins. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[46]  H. Schwalbe,et al.  Characterization of the unfolded state of bovine α‐lactalbumin and comparison with unfolded states of homologous proteins , 2006, Protein science : a publication of the Protein Society.

[47]  C. Micheletti,et al.  Convergent dynamics in the protease enzymatic superfamily. , 2006, Journal of the American Chemical Society.

[48]  Sarah A. Teichmann,et al.  3D Complex: A Structural Classification of Protein Complexes , 2006, PLoS Comput. Biol..

[49]  J. Marsh,et al.  Sensitivity of secondary structure propensities to sequence differences between alpha- and gamma-synuclein: implications for fibrillation. , 2006, Protein science : a publication of the Protein Society.

[50]  Frances H Arnold,et al.  Structural determinants of the rate of protein evolution in yeast. , 2006, Molecular biology and evolution.

[51]  J. Marsh,et al.  Sensitivity of secondary structure propensities to sequence differences between α‐ and γ‐synuclein: Implications for fibrillation , 2006 .

[52]  D. Thirumalai,et al.  Low-frequency normal modes that describe allosteric transitions in biological nanomachines are robust to sequence variations , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[53]  Joost Schymkowitz,et al.  The stability effects of protein mutations appear to be universally distributed. , 2007, Journal of molecular biology.

[54]  C. Robinson,et al.  Determining the stoichiometry and interactions of macromolecular assemblies from mass spectrometry , 2007, Nature Protocols.

[55]  Marc S. Cortese,et al.  Structural Basis for Regulation of Protein Phosphatase 1 by Inhibitor-2* , 2007, Journal of Biological Chemistry.

[56]  R. Milo,et al.  The relationship between evolutionary and physiological variation in hemoglobin , 2007, Proceedings of the National Academy of Sciences.

[57]  D. Thirumalai,et al.  Allosteric transitions in the chaperonin GroEL are captured by a dominant normal mode that is most robust to sequence variations. , 2007, Biophysical journal.

[58]  Giancarlo Mauri,et al.  Detecting similarities among distant homologous proteins by comparison of domain flexibilities. , 2007, Protein engineering, design & selection : PEDS.

[59]  J. Echave,et al.  Evolutionary conservation of protein vibrational dynamics. , 2008, Gene.

[60]  Modesto Orozco,et al.  Comparison of molecular dynamics and superfamily spaces of protein domain deformation , 2009, BMC Structural Biology.

[61]  S. Teichmann,et al.  Assembly reflects evolution of protein complexes , 2008, Nature.

[62]  A. Lesk,et al.  Correspondences between low‐energy modes in enzymes: Dynamics‐based alignment of enzymatic functional families , 2008, Protein science : a publication of the Protein Society.

[63]  M. Sternberg,et al.  Insights into protein flexibility: The relationship between normal modes and conformational change upon protein–protein docking , 2008, Proceedings of the National Academy of Sciences.

[64]  J. Doye,et al.  Self-assembly and evolution of homomeric protein complexes. , 2008, Physical review letters.

[65]  Jens Meiler,et al.  A Correspondence Between Solution-State Dynamics of an Individual Protein and the Sequence and Conformational Diversity of its Family , 2009, PLoS Comput. Biol..

[66]  Dan S. Tawfik,et al.  Protein Dynamism and Evolvability , 2009, Science.

[67]  Jotun Hein,et al.  Dynamics based alignment of proteins: an alternative approach to quantify dynamic similarity , 2010, BMC Bioinformatics.

[68]  Yu Xia,et al.  Structural determinants of protein evolution are context-sensitive at the residue level. , 2009, Molecular biology and evolution.

[69]  Peter F Stadler,et al.  Solvent exposure imparts similar selective pressures across a range of yeast proteins. , 2009, Molecular biology and evolution.

[70]  Christopher J. Oldfield,et al.  Do viral proteins possess unique biophysical features? , 2009, Trends in biochemical sciences.

[71]  Catherine L. Worth,et al.  Structural and functional constraints in the evolution of protein families , 2009, Nature Reviews Molecular Cell Biology.

[72]  L. Kay,et al.  Quaternary dynamics and plasticity underlie small heat shock protein chaperone function , 2010, Proceedings of the National Academy of Sciences.

[73]  M. Tyers,et al.  Structure/function implications in a dynamic complex of the intrinsically disordered Sic1 with the Cdc4 subunit of an SCF ubiquitin ligase. , 2010, Structure.

[74]  Gary D Bader,et al.  Bringing order to protein disorder through comparative genomics and genetic interactions , 2011, Genome Biology.

[75]  Comparing Models of Evolution for Ordered and Disordered Proteins , 2009, Molecular biology and evolution.

[76]  J. Marsh,et al.  Structural diversity in free and bound states of intrinsically disordered protein phosphatase 1 regulators. , 2010, Structure.

[77]  J. Echave,et al.  A perturbative view of protein structural variation , 2010, Proteins.

[78]  A. Panchenko,et al.  Mechanisms of protein oligomerization, the critical role of insertions and deletions in maintaining different oligomeric states , 2010, Proceedings of the National Academy of Sciences.

[79]  Tal Pupko,et al.  ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids , 2010, Nucleic Acids Res..

[80]  Benjamin A. Shoemaker,et al.  Evolution of protein binding modes in homooligomers. , 2010, Journal of molecular biology.

[81]  Francesca Fanelli,et al.  Deciphering the deformation modes associated with function retention and specialization in members of the Ras superfamily. , 2010, Structure.

[82]  Ivet Bahar,et al.  On the Conservation of the Slow Conformational Dynamics within the Amino Acid Kinase Family: NAGK the Paradigm , 2010, PLoS Comput. Biol..

[83]  A. Ramanathan,et al.  Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis , 2011, PLoS biology.

[84]  Thomas A. Hopf,et al.  Protein 3D Structure Computed from Evolutionary Sequence Variation , 2011, PloS one.

[85]  W. Taylor,et al.  Exploring the factors determining the dynamics of different protein folds , 2011, Protein Science.

[86]  Sarah A. Teichmann,et al.  Relative Solvent Accessible Surface Area Predicts Protein Conformational Changes upon Binding , 2011, Structure.

[87]  Jouhyun Jeon,et al.  Molecular evolution of protein conformational changes revealed by a network of evolutionarily coupled residues. , 2011, Molecular biology and evolution.

[88]  Dan S. Tawfik,et al.  Slow protein evolutionary rates are dictated by surface–core association , 2011, Proceedings of the National Academy of Sciences.

[89]  C. Sander,et al.  Direct-coupling analysis of residue coevolution captures native contacts across many protein families , 2011, Proceedings of the National Academy of Sciences.

[90]  Claus O Wilke,et al.  The Relationship Between Relative Solvent Accessibility and Evolutionary Rate in Protein Evolution , 2011, Genetics.

[91]  Subhajyoti De,et al.  Cellular crowding imposes global constraints on the chemistry and evolution of proteomes , 2012, Proceedings of the National Academy of Sciences.

[92]  D. Tobi.  Dynamics alignment: Comparison of protein dynamics in the scop database , 2012, Proteins.

[93]  Patrick Aloy,et al.  The Role of Structural Disorder in the Rewiring of Protein Interactions through Evolution* , 2012, Molecular & Cellular Proteomics.

[94]  Lucy J. Colwell,et al.  The interface of protein structure, protein biophysics, and molecular evolution , 2012, Protein science : a publication of the Protein Society.

[95]  S. Teichmann,et al.  Probing the diverse landscape of protein flexibility and binding. , 2012, Current opinion in structural biology.

[96]  Julián Echave,et al.  Why are the low-energy protein normal modes evolutionarily conserved? , 2012 .

[97]  Jan Kubelka,et al.  A Phylogenetic Analysis of Normal Modes Evolution in Enzymes and its Relationship to Enzyme Function , 2012 .

[98]  I. Bahar,et al.  Sequence Evolution Correlates with Structural Dynamics , 2012, Molecular biology and evolution.

[99]  C. Chothia,et al.  Evolution of oligomeric state through geometric coupling of protein interfaces , 2012, Proceedings of the National Academy of Sciences.

[100]  David T. Jones,et al.  Protein topology from predicted residue contacts , 2012, Protein science : a publication of the Protein Society.

[101]  K. Nakai,et al.  Chemical composition is maintained in poorly conserved intrinsically disordered regions and suggests a means for their classification. , 2012, Molecular bioSystems.

[102]  G. Vriend,et al.  Exploring Protein Dynamics Space: The Dynasome as the Missing Link between Protein Structure and Function , 2012, PloS one.

[103]  Joseph A Marsh,et al.  Ensemble modeling of protein disordered states: Experimental restraint contributions and validation , 2011, Proteins.

[104]  J. Tanner,et al.  Conservation of functionally important global motions in an enzyme superfamily across varying quaternary structures. , 2012, Journal of molecular biology.

[105]  Nicolas Doucet,et al.  Conservation of Flexible Residue Clusters among Structural and Functional Enzyme Homologues* , 2012, The Journal of Biological Chemistry.

[106]  Lucy J. Colwell,et al.  The emergence of protein complexes: quaternary structure, dynamics and allostery. Colworth Medal Lecture. , 2012, Biochemical Society transactions.

[107]  M. Blackledge,et al.  Describing intrinsically disordered proteins at atomic resolution by NMR. , 2013, Current opinion in structural biology.

[108]  L. Trinkle-Mulcahy,et al.  Novel methods for studying multiprotein complexes in vivo , 2013, F1000prime reports.

[109]  Hongwei Wu,et al.  Structural divergence is more extensive than sequence divergence for a family of intrinsically disordered proteins , 2013, Proteins.

[110]  S. Teichmann,et al.  The Role of Salt Bridges, Charge Density, and Subunit Flexibility in Determining Disassembly Routes of Protein Complexes , 2013, Structure.

[111]  Dan S. Tawfik,et al.  What makes a protein fold amenable to functional innovation? Fold polarity and stability trade-offs. , 2013, Journal of molecular biology.

[112]  J. Marsh.  Buried and accessible surface area control intrinsic protein flexibility. , 2013, Journal of molecular biology.

[113]  Alexandre M J J Bonvin,et al.  Molecular origins of binding affinity: seeking the Archimedean point. , 2013, Current opinion in structural biology.

[114]  Adam Godzik,et al.  Divergent evolution of protein conformational dynamics in dihydrofolate reductase , 2013, Nature Structural &Molecular Biology.

[115]  Diego J. Zea,et al.  Protein conformational diversity correlates with evolutionary rate. , 2013, Molecular biology and evolution.

[116]  Erich Bornberg-Bauer,et al.  Dynamics and adaptive benefits of modular protein evolution. , 2013, Current opinion in structural biology.

[117]  A Keith Dunker,et al.  Alternative splicing of intrinsically disordered regions and rewiring of protein interactions. , 2013, Current opinion in structural biology.

[118]  J. Forman-Kay,et al.  From sequence and forces to structure, function, and evolution of intrinsically disordered proteins. , 2013, Structure.

[119]  S. Teichmann,et al.  Protein Complexes Are under Evolutionary Selection to Assemble via Ordered Pathways , 2013, Cell.

[120]  Chris Neale,et al.  Characterization of disordered proteins with ENSEMBLE , 2013, Bioinform..

[121]  C. Micheletti.  Comparing proteins by their internal dynamics: exploring structure-function relationships beyond static structural alignments. , 2012, Physics of life reviews.