The Folding Transition State of the Cold Shock Protein is Strongly Polarized

Garcia-Mira, Maria M.; Boehringer, Daniel; Schmid, Franz X.

doi:10.1016/j.jmb.2004.04.011

Cited by 79 publications

(103 citation statements)

References 59 publications

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“…But ⌽ i is a good estimate of Q i for a particular moiety in a transition state. For the purposes of simulation of transition states, ⌽ values are divided into weak (Ͻ0.3), medium (0.3-0.6), and strong (Ͼ0.6) (16,52). In practice, a medium value of ⌽ means that the region has close to native-like topology and strong means that it is very close to full native structure as is intuitively obvious and as shown by simulation (20,53,54 …”

Section: Summary Of Interpretation Of Protein Folding Reaction Coordimentioning

confidence: 99%

Relationship of Leffler (Brønsted) α values and protein folding Φ values to position of transition-state structures on reaction coordinates

Fersht

2004

Proc. Natl. Acad. Sci. U.S.A.

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The positions of transition states along reaction coordinates ( r ‡ ) for simple chemical reactions are often estimated from Leffler α values, the slope of plots of Δ G ‡ (activation energy) versus Δ G 0 (equilibrium free energy) for a series of structural variants. Protein folding is more complex than simple chemical reactions and has a multitude of reaction coordinates. Φ-Value analysis measures degree of structure formation at individual residues in folding transition states from the ratio ΔΔ G ‡ /ΔΔ G 0 for mutations. α values are now being used to analyze protein folding by lumping series of Φ values into single plots. But, there are discrepancies in the values of α for folding with more classical measures of the extent of structure formation, which I rationalize here. I show for chemical reactions with just a single reaction coordinate that α = r ‡ only for limiting cases, such as for reactants and products being in parabolic energy wells of identical curvature. Otherwise, α can differ radically from r ‡ , with α being determined just by the angles of intersection of reactant and product energy surfaces. Φ is an index of the progress of a local, energy-based reaction coordinate at the global transition state: Φ <0.5 corresponds to <50% progress of the local coordinate at the global transition state and Φ >0.5 means >50%. Protein Leffler plots can force different local indexes to a single fit and give skewed underestimates of the extent of global structure formation in transition states that differ from other measures of structure formation.

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Section: Summary Of Interpretation Of Protein Folding Reaction Coordimentioning

confidence: 99%

Relationship of Leffler (Brønsted) α values and protein folding Φ values to position of transition-state structures on reaction coordinates

Fersht

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Interestingly, the sequence of folding events revealed by our simulations is essentially in the reverse order of unfolding simulations at high temperature. 28 The TS is more compact than that suggested by experimental f-value analysis 7 and theory. 24 The mutation study of F20 and F31 for Csp from E. coli 13 suggested that these two residues should be present in the TS, that is, b2 and b3 might folded.…”

Section: The Folding Mechanism Of Cspmentioning

confidence: 87%

“…Perl et al 9 have proposed that the N-terminal region is folded but the C-terminal is not in the TS. Furthermore, Garcia-Mira et al 7 suggested that the development of native contacts between b1 and b4 is crucial for reaching the TS. It seems that the TSE identified by this study is consistent with most experiments.…”

Section: The Folding Mechanism Of Cspmentioning

confidence: 99%

“…The dependence of rate constants of refolding and unfolding on denaturant concentration suggests that the transition state (TS) of Csp should be very compact. [3][4][5][6][7][9][10][11][12][13]15 On the other hand, f-value analysis, proposed by Fersht et.al., 23 has served as a powerful method to study the TSE. So far, f-value analysis has been used to systematically study the TSE of Csp from B. subtilis.…”

Section: Introductionmentioning

confidence: 99%

“…So far, f-value analysis has been used to systematically study the TSE of Csp from B. subtilis. 7 They suggested that in the TS b1 resembles the structure in folded state, the hairpin by b1-b2 is formed, the hairpin by b2-b3 is partially formed, and native contacts between b1-b4 are partially developed. This is partially consistent with the TS suggested by Alm et al, 24 who proposed that b1-b2-b3 form a well-ordered structure and the native contacts in the loop between b3 and b4 are partially developed.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Is there an en route folding intermediate for cold shock proteins?

Huang

Shakhnovich

2012

Protein Science

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Cold shock proteins (Csps) play an important role in cold shock response of a diverse number of organisms ranging from bacteria to humans. Numerous studies of the Csp from various species showed that a two-state folding mechanism is conserved and the transition state (TS) appears to be very compact. However, the atomic details of the folding mechanism of Csp remain unclear. This study presents the folding mechanism of Csp in atomic detail using an all-atom Go model-based simulations. Our simulations predict that there may exist an en route intermediate, in which b strands 1-2-3 are well ordered and the contacts between b1 and b4 are almost developed. Such an intermediate might be too unstable to be detected in the previous fluorescence energy transfer experiments. The transition state ensemble has been determined from the P fold analysis and the TS appears even more compact than the intermediate state.

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Overview of Protein Folding Mechanisms: Experimental and Theoretical Approaches to Probing Energy Landscapes

Morris

Searle

2012

CP Protein Science

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We present an overview of the current experimental and theoretical approaches to studying protein folding mechanisms, set against current models of the folding energy landscape. We describe how stability and folding kinetics can be determined experimentally and how this data can be interpreted in terms of the characteristic features of various models from the simplest two-state pathway to a multi-state mechanism. We summarize the pros and cons of a range of spectroscopic methods for measuring folding rates and present a theoretical framework, coupled with protein engineering approaches, for elucidating folding mechanisms and structural features of folding transition states. A series of case studies are used to show how experimental kinetic data can be interpreted in the context of non-native interactions, populated intermediates, parallel folding pathways, and sequential transition states. We also show how computational methods now allow transient species of high energy, such as folding transition states, to be modeled on the basis of experimental Φ-value analysis derived from the effects of point mutations on folding kinetics.

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The Folding Transition State of the Cold Shock Protein is Strongly Polarized

Cited by 79 publications

References 59 publications

Relationship of Leffler (Brønsted) α values and protein folding Φ values to position of transition-state structures on reaction coordinates

Relationship of Leffler (Brønsted) α values and protein folding Φ values to position of transition-state structures on reaction coordinates

Is there an en route folding intermediate for cold shock proteins?

Overview of Protein Folding Mechanisms: Experimental and Theoretical Approaches to Probing Energy Landscapes

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