Folding kinetics of Che Y mutants with enhanced native α-helix propensities 1 1Edited by A. R. Fersht

López-Hernández, Eva; Cronet, Philippe; Serrano, Luís; Muñoz, Víctor

doi:10.1006/jmbi.1996.0793

Cited by 63 publications

(54 citation statements)

References 39 publications

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“…What, then, is the required role of helicity along the pathway? Many experiments have demonstrated that enhancing intrinsic helicity accelerates folding (2,4,(16)(17)(18)(19)(20)(21). Such strengthening stabilizes all conformations containing helix, including the transition state (Fig.…”

Section: Gcn4-e9g4 Folding Pathwaymentioning

confidence: 99%

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Fast folding of a helical protein initiated by the collision of unstructured chains

Meisner

Sosnick

2004

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

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To examine whether helix formation necessarily precedes chain collision, we have measured the folding of a fully helical coiled coil that has been specially engineered to have negligible intrinsic helical propensity but high overall stability. The folding rate approaches the diffusion-limited value and is much faster than possible if folding is contingent on precollision helix formation. Therefore, the collision of two unstructured chains is the initial step of the dominant kinetic pathway, whereas helicity exerts its influence only at a later step. Folding from an unstructured encounter complex may be efficient and robust, which has implications for any biological process that couples folding to binding.ne of the most debated issues in protein folding concerns the earliest folding events leading up to the transition state (1-9). For helical proteins, the earliest productive folding steps often are postulated to involve the collision of two preformed, but not necessarily stable, helical elements, rather than collision of unstructured chains. This diffusion-collision model (D-C model) (10-12) is supported by the observation that helix formation is faster than overall folding rates (13-15). This broadly accepted view also is supported by the presence of helix in the folding transition state and an increase in k f with an increase in helical propensity (2, 4, 16-21).However, this correlation can support an opposing model in which unstructured chains first collide, and the enhanced helicity increases the success frequency (or transmission coefficient) of each encounter (Fig. 1). In general, the highly cooperative (two-state) folding behavior of most small proteins precludes identifying the order of events leading up to the kinetic barrier. As a result, the demonstration of helical structure in the transition state cannot by itself resolve whether helix formation or chain collision occurs first.This obstacle can be overcome by studying a system with minimal helical propensity and composed of more than one chain, so that the rate of collision can be varied (22). These properties enable comparisons between observed folding rates and the maximum rate consistent with a model where precollision helix formation is required. Our investigation uses this strategy in conjunction with a dimeric coiled coil protein specially engineered to have negligible intrinsic helicity but high stability. This protein folds at nearly the diffusion limit and certainly at a much faster rate than would be possible if the helix must form before collision. Thus, an unstructured encounter complex can successfully initiate rapid folding, with helix formation occurring at a later step. The collision-first route sets a high basal level for the folding rate of any protein.

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Section: Gcn4-e9g4 Folding Pathwaymentioning

confidence: 99%

“…This diffusion-collision model (D-C model) (10)(11)(12) is supported by the observation that helix formation is faster than overall folding rates (13)(14)(15). This broadly accepted view also is supported by the presence of helix in the folding transition state and an increase in k f with an increase in helical propensity (2,4,(16)(17)(18)(19)(20)(21).…”

mentioning

confidence: 91%

Fast folding of a helical protein initiated by the collision of unstructured chains

Meisner

Sosnick

2004

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

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“…Analysis of the folding kinetics suggests that all five helices of CheY are formed in this sub-millisecond species (118). The far-UV CD spectrum of this intermediate resembles that of the native state.…”

Section: Folding Of Proteins That Share the Flavodoxin-like Fold: Thementioning

confidence: 88%

“…Indeed, this off-pathway species is largely α-helical (69). The off-pathway intermediate of CheY also appears to be helical, as all five native α-helices are formed and as stabilization of any of its α-helices slows refolding at low denaturant concentrations (118). Experiments thus strongly suggest that the off-pathway intermediate of flavodoxin-like proteins is of helical nature.…”

Section: Flavodoxin-like Proteins Tend To Temporarily Misfold During mentioning

confidence: 97%

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The ribosome regulates flavodoxin folding

Houwman¹

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Major differences in stability and dimerization properties of two chimeric mutants of human stefins

et al. 2001

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Folding kinetics of Che Y mutants with enhanced native α-helix propensities 1 1Edited by A. R. Fersht

Cited by 63 publications

References 39 publications

Fast folding of a helical protein initiated by the collision of unstructured chains

Fast folding of a helical protein initiated by the collision of unstructured chains

The ribosome regulates flavodoxin folding

Major differences in stability and dimerization properties of two chimeric mutants of human stefins

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