Topology, stability, sequence, and length: defining the determinants of two-state protein folding kinetics

TitleTopology, stability, sequence, and length: defining the determinants of two-state protein folding kinetics
Publication TypeJournal Article
Year of Publication2000
AuthorsPlaxco, K. W., Simons K. T., Ruczinski I., & Baker D.
JournalBiochemistry
Volume39
Issue37
Pagination11177-83
Date Published2000 Sep 19
ISSN0006-2960
KeywordsAmino Acid Sequence, Animals, Humans, Kinetics, Models, Chemical, Primary Publication, Protein Folding, Proteins, Structure-Activity Relationship, Thermodynamics
Abstract

The fastest simple, single domain proteins fold a million times more rapidly than the slowest. Ultimately this broad kinetic spectrum is determined by the amino acid sequences that define these proteins, suggesting that the mechanisms that underlie folding may be almost as complex as the sequences that encode them. Here, however, we summarize recent experimental results which suggest that (1) despite a vast diversity of structures and functions, there are fundamental similarities in the folding mechanisms of single domain proteins and (2) rather than being highly sensitive to the finest details of sequence, their folding kinetics are determined primarily by the large-scale, redundant features of sequence that determine a protein's gross structural properties. That folding kinetics can be predicted using simple, empirical, structure-based rules suggests that the fundamental physics underlying folding may be quite straightforward and that a general and quantitative theory of protein folding rates and mechanisms (as opposed to unfolding rates and thus protein stability) may be near on the horizon.

Alternate JournalBiochemistry
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