Journal ArticleDOI
Folding dynamics of the src sh3 domain
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TLDR
Comparison of the src SH3 with homologous SH3 domains as well as with other small well-characterized beta-sheet proteins provides insights into the determinants of folding kinetics and protein stability.Abstract:
The thermodynamics and kinetics of folding of the chicken src SH3 domain were characterized using equilibrium and stopped-flow fluorescence, circular dichroism (CD), and nuclear magnetic resonance (NMR) hydrogen exchange experiments As found for other SH3 domains, guanidinium chloride (GdmCl) denaturation melts followed by both fluorescence and circular dichroism were nearly superimposable, indicating the concerted formation of secondary and tertiary structure Kinetic studies confirmed the two-state character of the folding reaction Except for a very slow refolding phase due to proline isomerization, both folding and unfolding traces fit well to single exponentials over a wide range of GdmCl concentrations, and no burst phase in amplitude was observed during the dead time of the stopped-flow instrument The entropy, enthalpy, and heat capacity changes upon unfolding were determined by global fitting of temperature melts at varying GdmCl concentrations (04−37 M) Estimates of the free energy of unfoldread more
Citations
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Contact order, transition state placement and the refolding rates of single domain proteins
TL;DR: Investigations have revealed statistically significant correlations between the average sequence separation between contacting residues in the native state and the rate and transition state placement of folding for a non-homologous set of simple, single domain proteins, indicating that proteins featuring primarily sequence-local contacts tend to fold more rapidly and exhibit less compact folding transition states than those characterized by more non-local interactions.
Journal ArticleDOI
How do small single-domain proteins fold?
TL;DR: Using recent studies, can the authors begin to search for trends which may lead to a better understanding of the protein folding process, and stable intermediates are not a prerequisite for the fast, efficient folding of proteins.
Journal ArticleDOI
Amyloid fibril formation by an SH3 domain
TL;DR: Results indicate that the A state of PI3-SH3 is partially folded and support the hypothesis that partially folded states formed in solution are precursors of amyloid deposition.
Journal ArticleDOI
From folding theories to folding proteins: a review and assessment of simulation studies of protein folding and unfolding.
Joan-Emma Shea,Charles L. Brooks +1 more
TL;DR: Assessment of the two methods suggests that both can provide, often complementary, details of folding mechanism and thermodynamics, but this success relies on adequate sampling of diverse conformational regions for the biased-sampling free energy approach and many trajectories at multiple temperatures for unfolding studies.
Journal ArticleDOI
Experiment and theory highlight role of native state topology in SH3 folding.
David S. Riddle,David S. Riddle,Viara P. Grantcharova,Jed V. Santiago,Eric J. Alm,Ingo Ruczinski,David Baker +6 more
TL;DR: Kinetic analysis of mutations at 52 of the 57 residues in the src SH3 domain revealed that the transition state ensemble is even more polarized than suspected, and the similarity in folding mechanism of different SH3 domains and the similar hierarchy of structure formation observed in the experiments and the simulations can be largely accounted for by a simple native state topology-based model of protein folding energy landscapes.
References
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Journal ArticleDOI
Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions
TL;DR: The effects of multiple sequence information and different types of conformational constraints on the overall performance of the method are investigated, and the ability of a variety of recently developed scoring functions to recognize the native-like conformations in the ensembles of simulated structures are investigated.
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Backbone 1H and 15N resonance assignments of the N-terminal SH3 domain of drk in folded and unfolded states using enhanced-sensitivity pulsed field gradient NMR techniques
TL;DR: NMR methods which exploit the chemical shift dispersion of the 15N resonances of unfolded states and pulsed field gradient water suppression approaches for avoiding saturation and dephasing of amide protons which rapidly exchange with solvent were utilized for the assignment.
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Structures of SH2 and SH3 domains
TL;DR: The recent determination of the three-dimensional structures of several SH2 and SH3 domains has led to considerable progress in understanding their mechanism of action, and these structures are the focus of this review.
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Hydrogen exchange in chymotrypsin inhibitor 2 probed by denaturants and temperature.
TL;DR: In this article, the authors measured hydrogen exchange of chymotrypsin inhibitor 2 in the presence of low concentrations of GDMCl and at different temperatures, and obtained the activation enthalpies for the local exchange processes, and the change in enthalpy between the closed, exchangeincompetent, forms and the open, exchange-competant, forms.
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Conformational Analysis of Peptides Corresponding to β-Hairpins and a β-Sheet that Represent the Entire Sequence of the α-Spectrin SH3 Domain
TL;DR: In this paper, the authors examined conformational preferences in aqueous solution of peptides that span the entire length of the α-spectrin SH3 domain, using proton nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy.