Effects of varying the local propensity to form secondary structure on the stability and folding kinetics of a rapid folding mixed α/β protein: characterization of a truncation mutant of the N-terminal domain of the ribosomal protein L9 1 1Edited by P. E. Wright

Luisi, Donna L.; Kuhlman, Brian; Sideras, Kostandinos; Evans, Philip A.; Raleigh, Daniel P.

doi:10.1006/jmbi.1999.2742

Cited by 27 publications

(30 citation statements)

References 28 publications

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“…32,33 The fragment lacks the C-terminal α-helix; however, experimental work has shown that formation of this helix and its docking to the β-α-β core is not part of the rate-limiting step in the folding of NTL9. 34 Horng et al chose to study the K12M mutant since it folds faster, 33 making it more attractive for computational studies; however, the folding rate is of the same magnitude as that of wild-type NTL9 1-39 . The calculations were approximate since the implicit solvent model used did not change with temperature; that is, it had not been parameterized to reproduce the temperature dependence of the hydrophobic effect and solvent properties.…”

Section: Discussionmentioning

confidence: 98%

Temperature-Dependent Hammond Behavior in a Protein-Folding Reaction: Analysis of Transition-State Movement and Ground-State Effects

Taskent

Cho

Raleigh

2008

Journal of Molecular Biology

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Characterization of the transition-state ensemble and the nature of the free-energy barrier for protein folding are areas of intense activity and some controversy. A key issue that has emerged in recent years is the width of the free-energy barrier and the susceptibility of the transition state to movement. Here we report denaturant-induced and temperature-dependent folding studies of a small mixed alpha-beta protein, the N-terminal domain of L9 (NTL9). The folding of NTL9 was determined using fluorescence-detected stopped-flow fluorescence measurements conducted at seven different temperatures between 11 and 40 degrees C. Plots of the log of the observed first-order rate constant versus denaturant concentration, "chevron plots," displayed the characteristic V shape expected for two-state folding. There was no hint of deviation from linearity even at the lowest denaturant concentrations. The relative position of the transition state, as judged by the Tanford beta parameter, beta(T), shifts towards the native state as the temperature is increased. Analysis of the temperature dependence of the kinetic and equilibrium m values indicates that the effect is due to significant movement of the transition state and also includes a contribution from temperature-dependent ground-state effects. Analysis of the Leffler plots, plots of Delta G versus Delta G degrees, and their cross-interaction parameters confirms the transition-state movement. Since the protein is destabilized at high temperature, the shift represents a temperature-dependent Hammond effect. This provides independent confirmation of a recent theoretical prediction. The magnitude of the temperature-denaturant cross-interaction parameter is larger for NTL9 than has been reported for the few other cases studied. The implications for temperature-dependent studies of protein folding are discussed.

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Section: Discussionmentioning

confidence: 98%

Temperature-Dependent Hammond Behavior in a Protein-Folding Reaction: Analysis of Transition-State Movement and Ground-State Effects

Taskent

Cho

Raleigh

2008

Journal of Molecular Biology

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“…The relative importance of secondary versus tertiary interactions in determining folding rates was studied experimentally for a number of proteins, including the activation domain of carboxypeptyidase A (CPA) (84), CheY (84), the helical coiled-coil GCN4 (32,82,85,116), GB1 domain (19), its structural homologue protein L (57a), λ-repressor (12), and ribosomal protein L9 (73). In all cases, secondary interactions play no role or only a minor one in determining folding kinetics.…”

Section: Diffusion-collision Mechanismmentioning

confidence: 99%

Protein Folding Theory: From Lattice to All-Atom Models

Mirny

Shakhnovich

2001

Annu. Rev. Biophys. Biomol. Struct.

330

259

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This review focuses on recent advances in understanding protein folding kinetics in the context of nucleation theory. We present basic concepts such as nucleation, folding nucleus, and transition state ensemble and then discuss recent advances and challenges in theoretical understanding of several key aspects of protein folding kinetics. We cover recent topology-based approaches as well as evolutionary studies and molecular dynamics approaches to determine protein folding nucleus and analyze other aspects of folding kinetics. Finally, we briefly discuss successful all-atom Monte-Carlo simulations of protein folding and conclude with a brief outlook for the future.

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“…85,86 In the present study, we compare the folding cooperativity of NTL9 and two homologous peripheral subunitbinding domain (PSBD) proteins (PDB IDs: 1W4E and 2BTH), for which experimental structural and folding data are available. 30,32,73,87 Among these three proteins, each of the two PSBD proteins has a clearly different native topology from that of NTL9, whereas the two PSBD homologs have essentially identical folds with only subtle differences in packing. Application of our approach outlined above suggests strongly that native topology is predictive of and probably constraining on folding cooperativity.…”

Section: Introductionmentioning

confidence: 98%

Probing Possible Downhill Folding: Native Contact Topology Likely Places a Significant Constraint on the Folding Cooperativity of Proteins with ∼40 Residues

Badasyan

Liu

Chan

2008

Journal of Molecular Biology

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Effects of varying the local propensity to form secondary structure on the stability and folding kinetics of a rapid folding mixed α/β protein: characterization of a truncation mutant of the N-terminal domain of the ribosomal protein L9 1 1Edited by P. E. Wright

Cited by 27 publications

References 28 publications

Temperature-Dependent Hammond Behavior in a Protein-Folding Reaction: Analysis of Transition-State Movement and Ground-State Effects

Temperature-Dependent Hammond Behavior in a Protein-Folding Reaction: Analysis of Transition-State Movement and Ground-State Effects

Protein Folding Theory: From Lattice to All-Atom Models

Probing Possible Downhill Folding: Native Contact Topology Likely Places a Significant Constraint on the Folding Cooperativity of Proteins with ∼40 Residues

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