Take home lessons from studies of related proteins

Highlights ► We review the recent advances made from the study of related proteins. ► We relate pathway malleability to the balance between foldons and helical propensity. ► We speculate why different topologies respond differently to mutation. ► We discuss the role of kinetic intermediates in folding pathways. ► We explain why it is important to study several members from each protein fold.

[1]  O. Ptitsyn,et al.  Alpha-Lactalbumin: compact state with fluctuating tertiary structure? , 1981, FEBS letters.

[2]  Jane Clarke,et al.  Separating the effects of internal friction and transition state energy to explain the slow, frustrated folding of spectrin domains , 2012, Proceedings of the National Academy of Sciences.

[3]  D. Baker,et al.  Contact order, transition state placement and the refolding rates of single domain proteins. , 1998, Journal of molecular biology.

[4]  Doug Barrick,et al.  The contribution of entropy, enthalpy, and hydrophobic desolvation to cooperativity in repeat-protein folding. , 2011, Structure.

[5]  David Baker,et al.  Computer-based redesign of a protein folding pathway , 2001, Nature Structural Biology.

[6]  Ronald D. Hills,et al.  Topological frustration in beta alpha-repeat proteins: sequence diversity modulates the conserved folding mechanisms of alpha/beta/alpha sandwich proteins. , 2010, Journal of molecular biology.

[7]  Valerie Daggett,et al.  The Denatured State Dictates the Topology of Two Proteins with Almost Identical Sequence but Different Native Structure and Function* , 2010, The Journal of Biological Chemistry.

[8]  Valerie Daggett,et al.  Folding mechanisms of proteins with high sequence identity but different folds. , 2007, Biochemistry.

[9]  Peter G Wolynes,et al.  Latest folding game results: protein A barely frustrates computationalists. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  E. Paci,et al.  Comparison of the transition states for folding of two Ig-like proteins from different superfamilies. , 2004, Journal of molecular biology.

[11]  Jane Clarke,et al.  What lessons can be learned from studying the folding of homologous proteins? , 2010, Methods.

[12]  Jane Clarke,et al.  Topology is the Principal Determinant in the Folding of a Complex All-alpha Greek Key Death Domain from Human FADD , 2009, Journal of molecular biology.

[13]  D. Wetlaufer Nucleation, rapid folding, and globular intrachain regions in proteins. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Clarke,et al.  Different Members of a Simple Three-Helix Bundle Protein Family Have Very Different Folding Rate Constants and Fold by Different Mechanisms , 2009, Journal of molecular biology.

[15]  E I Shakhnovich,et al.  Folding nucleus: specific or multiple? Insights from lattice models and experiments. , 1998, Folding & design.

[16]  M. Karplus,et al.  Protein-folding dynamics , 1976, Nature.

[17]  E. Paci,et al.  Mechanical unfolding of a titin Ig domain: structure of transition state revealed by combining atomic force microscopy, protein engineering and molecular dynamics simulations. , 2003, Journal of molecular biology.

[18]  R. Hosur,et al.  Conserved structural and dynamics features in the denatured states of drosophila SUMO, human SUMO and ubiquitin proteins: Implications to sequence‐folding paradigm , 2009, Proteins.

[19]  D. Baker,et al.  Critical role of β-hairpin formation in protein G folding , 2000, Nature Structural Biology.

[20]  K. Lindorff-Larsen,et al.  Parallel protein-unfolding pathways revealed and mapped , 2003, Nature Structural Biology.

[21]  O. Ptitsyn,et al.  α‐lactalbumin: compact state with fluctuating tertiary structure? , 1981, FEBS letters.

[22]  A. Fersht,et al.  Malleability of folding intermediates in the homeodomain superfamily , 2011, Proceedings of the National Academy of Sciences.

[23]  Valerie Daggett,et al.  Dynameomics: a consensus view of the protein unfolding/folding transition state ensemble across a diverse set of protein folds. , 2009, Biophysical journal.

[24]  Jane Clarke,et al.  Experimental evidence for a frustrated energy landscape in a 3-helix bundle protein family , 2009, Nature.

[25]  M. Oliveberg,et al.  Malleability of protein folding pathways: a simple reason for complex behaviour. , 2007, Current opinion in structural biology.

[26]  M. Akke,et al.  From snapshot to movie: phi analysis of protein folding transition states taken one step further. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Sophie E Jackson,et al.  The folding and design of repeat proteins: reaching a consensus. , 2003, Current opinion in structural biology.

[28]  Scattered Hammond plots reveal second level of site-specific information in protein folding: phi' (beta++). , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M. Karplus,et al.  Three key residues form a critical contact network in a protein folding transition state , 2001, Nature.

[30]  A. Fersht,et al.  Folding of chymotrypsin inhibitor 2. 1. Evidence for a two-state transition. , 1991, Biochemistry.

[31]  C Chothia,et al.  Conservation of folding and stability within a protein family: the tyrosine corner as an evolutionary cul-de-sac. , 2000, Journal of molecular biology.

[32]  J. Clarke,et al.  Folding of a LysM Domain: Entropy-Enthalpy Compensation in the Transition State of an Ideal Two-state Folder , 2008, Journal of molecular biology.

[33]  A. Fersht,et al.  Searching for multiple folding pathways of a nearly symmetrical protein: temperature dependent phi-value analysis of the B domain of protein A. , 2007, Journal of molecular biology.

[34]  Jane Clarke,et al.  Localizing internal friction along the reaction coordinate of protein folding by combining ensemble and single-molecule fluorescence spectroscopy , 2012, Nature Communications.

[35]  Sheena E. Radford,et al.  Im7 folding mechanism: misfolding on a path to the native state , 2002, Nature Structural Biology.

[36]  D Baker,et al.  Critical role of beta-hairpin formation in protein G folding. , 2000, Nature structural biology.

[37]  M. Karplus,et al.  Transition state contact orders correlate with protein folding rates. , 2005, Journal of molecular biology.

[38]  J. Clarke,et al.  Mapping the folding pathway of an immunoglobulin domain: structural detail from Phi value analysis and movement of the transition state. , 2001, Structure.

[39]  D. Baker,et al.  Principles for designing ideal protein structures , 2012, Nature.

[40]  Doug Barrick,et al.  Rerouting the folding pathway of the Notch ankyrin domain by reshaping the energy landscape. , 2008, Journal of the American Chemical Society.

[41]  Eugene I Shakhnovich,et al.  Identification of the minimal protein-folding nucleus through loop-entropy perturbations. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Per Jemth,et al.  Folding pathways of proteins with increasing degree of sequence identities but different structure and function , 2012, Proceedings of the National Academy of Sciences.

[43]  Sheena E Radford,et al.  Switching two-state to three-state kinetics in the helical protein Im9 via the optimisation of stabilising non-native interactions by design. , 2004, Journal of molecular biology.

[44]  Alan R. Lowe,et al.  Biophysical characterisation of the small ankyrin repeat protein myotrophin. , 2007, Journal of molecular biology.

[45]  D Baker,et al.  A breakdown of symmetry in the folding transition state of protein L. , 2000, Journal of molecular biology.

[46]  J. Boyer,et al.  Swapping core residues in homologous proteins swaps folding mechanism. , 2005, Biochemistry.

[47]  S. Teichmann,et al.  The folding and evolution of multidomain proteins , 2007, Nature Reviews Molecular Cell Biology.

[48]  S Walter Englander,et al.  Protein folding: the stepwise assembly of foldon units. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Pietro Faccioli,et al.  The Role of Non-Native Interactions in the Folding of Knotted Proteins , 2012, PLoS Comput. Biol..

[50]  E. Meiering,et al.  Conserved and nonconserved features of the folding pathway of hisactophilin, a β‐trefoil protein , 2002, Protein science : a publication of the Protein Society.

[51]  T. Kiefhaber,et al.  Three-state model for lysozyme folding: triangular folding mechanism with an energetically trapped intermediate. , 1997, Journal of molecular biology.

[52]  Valerie Daggett,et al.  Simulation and experiment conspire to reveal cryptic intermediates and a slide from the nucleation-condensation to framework mechanism of folding. , 2005, Journal of molecular biology.

[53]  Ellinor Haglund,et al.  Changes of Protein Folding Pathways by Circular Permutation , 2008, Journal of Biological Chemistry.

[54]  A R Panchenko,et al.  The foldon universe: a survey of structural similarity and self-recognition of independently folding units. , 1997, Journal of molecular biology.

[55]  Suganthi Balasubramanian,et al.  Protein alchemy: Changing β-sheet into α-helix , 1997, Nature Structural Biology.

[56]  Neil Ferguson,et al.  The folding mechanism of BBL: Plasticity of transition-state structure observed within an ultrafast folding protein family. , 2009, Journal of molecular biology.

[57]  S. Marqusee,et al.  The folding trajectory of RNase H is dominated by its topology and not local stability: a protein engineering study of variants that fold via two-state and three-state mechanisms. , 2009, Journal of molecular biology.

[58]  S. Marqusee,et al.  Destabilization of the Escherichia coli RNase H kinetic intermediate: switching between a two-state and three-state folding mechanism. , 2004, Journal of molecular biology.

[59]  M. Brunori,et al.  Unveiling a Hidden Folding Intermediate in c-Type Cytochromes by Protein Engineering* , 2006, Journal of Biological Chemistry.

[60]  A. Fersht,et al.  Folding of circular and permuted chymotrypsin inhibitor 2: retention of the folding nucleus. , 1998, Biochemistry.

[61]  Jane Clarke,et al.  The folding of spectrin domains II: phi-value analysis of R16. , 2004, Journal of molecular biology.

[62]  E. Paci,et al.  Non-Native Interactions Are Critical for Mechanical Strength in PKD Domains , 2009, Structure.

[63]  C. V. van Mierlo,et al.  Protein topology affects the appearance of intermediates during the folding of proteins with a flavodoxin-like fold. , 2005, Biophysical chemistry.

[64]  Luis Serrano,et al.  Different folding transition states may result in the same native structure , 1996, Nature Structural Biology.

[65]  K. Freed,et al.  Quantifying the structural requirements of the folding transition state of protein A and other systems. , 2008, Journal of molecular biology.

[66]  Yun-Ru Chen,et al.  Substitutions of prolines examine their role in kinetic trap formation of the caspase recruitment domain (CARD) of RICK , 2006, Protein science : a publication of the Protein Society.

[67]  J. Clarke,et al.  Plasticity Within the Obligatory Folding Nucleus of an Immunoglobulin-like Domain , 2008, Journal of molecular biology.

[68]  Stephen J. Moran,et al.  The folding pathway of spectrin R17 from experiment and simulation: using experimentally validated MD simulations to characterize States hinted at by experiment. , 2006, Journal of molecular biology.

[69]  Sophie E Jackson,et al.  Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins. , 2012, Nature chemical biology.

[70]  A. Fersht,et al.  The structure of the transition state for folding of chymotrypsin inhibitor 2 analysed by protein engineering methods: evidence for a nucleation-condensation mechanism for protein folding. , 1995, Journal of molecular biology.

[71]  Alan R Lowe,et al.  Rational redesign of the folding pathway of a modular protein , 2007, Proceedings of the National Academy of Sciences.

[72]  M. J. Parker,et al.  Effects of core mutations on the folding of a beta-sheet protein: implications for backbone organization in the I-state. , 1999, Biochemistry.

[73]  Valerie Daggett,et al.  Unifying features in protein-folding mechanisms , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[74]  M. Brunori,et al.  The folding pathway of an engineered circularly permuted PDZ domain. , 2008, Protein engineering, design & selection : PEDS.

[75]  A. Fersht,et al.  Towards the complete structural characterization of a protein folding pathway: the structures of the denatured, transition and native states for the association/folding of two complementary fragments of cleaved chymotrypsin inhibitor 2. Direct evidence for a nucleation-condensation mechanism. , 1996, Folding & design.

[76]  D. Barrick,et al.  The leucine-rich repeat domain of Internalin B folds along a polarized N-terminal pathway. , 2008, Structure.

[77]  Jeanette Tångrot,et al.  Complete change of the protein folding transition state upon circular permutation , 2002, Nature Structural Biology.

[78]  Sophie E Jackson,et al.  A comparison of the folding of two knotted proteins: YbeA and YibK. , 2007, Journal of molecular biology.

[79]  J. Clarke,et al.  The folding of an immunoglobulin-like Greek key protein is defined by a common-core nucleus and regions constrained by topology. , 2000, Journal of molecular biology.

[80]  M. Selmer,et al.  The Plastic Energy Landscape of Protein Folding , 2010, The Journal of Biological Chemistry.

[81]  Sheena E Radford,et al.  Structural analysis of the rate-limiting transition states in the folding of Im7 and Im9: similarities and differences in the folding of homologous proteins. , 2003, Journal of molecular biology.

[82]  J. Clarke,et al.  Protein Folding: Adding a Nucleus to Guide Helix Docking Reduces Landscape Roughness , 2012, Journal of molecular biology.

[83]  K. Itoh,et al.  Flexibly varying folding mechanism of a nearly symmetrical protein: B domain of protein A. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[84]  V. Mesyanzhinov,et al.  The carboxy-terminal domain initiates trimerization of bacteriophage T4 fibritin. , 1999, Biochemistry. Biokhimiia.

[85]  S. Marqusee,et al.  Identification of residual structure in the unfolded state of ribonuclease H1 from the moderately thermophilic Chlorobium tepidum: comparison with thermophilic and mesophilic homologues. , 2010, Biochemistry.

[86]  Valerie Daggett,et al.  The complete folding pathway of a protein from nanoseconds to microseconds , 2003, Nature.

[87]  Leslie L. Chavez,et al.  Multiple routes lead to the native state in the energy landscape of the β-trefoil family , 2006, Proceedings of the National Academy of Sciences.

[88]  E. Cota,et al.  The folding nucleus of a fibronectin type III domain is composed of core residues of the immunoglobulin-like fold. , 2001, Journal of molecular biology.

[89]  S. Balasubramanian,et al.  Protein alchemy: changing beta-sheet into alpha-helix. , 1997, Nature structural biology.

[90]  John Orban,et al.  NMR structures of two designed proteins with high sequence identity but different fold and function , 2008, Proceedings of the National Academy of Sciences.

[91]  P. M. Dalessio,et al.  Beta-sheet proteins with nearly identical structures have different folding intermediates. , 2000, Biochemistry.