Simulation of Top7-CFr: A transient helix extension guides folding

Document Type

Article

Publication Date

6-10-2008

Abstract

Protein structures often feature β-sheets in which adjacent β-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 β-strands at the N and C termini are neighbors in a β-sheet. The N-terminal β-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 β-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. © 2008 by The National Academy of Sciences of the USA.

Publication Title

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

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