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Simulation of Top7-CFr: a transient helix extension guides folding.

ABSTRACT: Protein structures often feature beta-sheets in which adjacent beta-strands have large sequence separation. How the folding process orchestrates the formation and correct arrangement of these strands is not comprehensively understood. Particularly challenging are proteins in which beta-strands at the N and C termini are neighbors in a beta-sheet. The N-terminal beta-strand is synthesized early on, but it can not bind to the C terminus before the chain is fully synthesized. During this time, there is a danger that the beta-strand at the N terminus interacts with nearby molecules, leading to potentially harmful aggregates of incompletely folded proteins. Simulations of the C-terminal fragment of Top7 show that this risk of misfolding and aggregation can be avoided by a "caching" mechanism that relies on the "chameleon" behavior of certain segments.

SUBMITTER: Mohanty S

PROVIDER: S-EPMC2786944 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Simulation of Top7-CFr: a transient helix extension guides folding.

Mohanty Sandipan S Meinke Jan H JH Zimmermann Olav O Hansmann Ulrich H E UH

Proceedings of the National Academy of Sciences of the United States of America 20080411 23

Protein structures often feature beta-sheets in which adjacent beta-strands have large sequence separation. How the folding process orchestrates the formation and correct arrangement of these strands is not comprehensively understood. Particularly challenging are proteins in which beta-strands at the N and C termini are neighbors in a beta-sheet. The N-terminal beta-strand is synthesized early on, but it can not bind to the C terminus before the chain is fully synthesized. During this time, ther ...[more]

PMID: 18408166

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