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Mechanism of protein folding
Author(s) -
Nölting Bengt,
Andert Karl
Publication year - 2000
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/1097-0134(20001115)41:3<288::aid-prot20>3.0.co;2-c
Subject(s) - barnase , protein secondary structure , chemistry , protein tertiary structure , protein folding , crystallography , molecule , protein structure , folding (dsp implementation) , biophysics , stereochemistry , biology , biochemistry , ribonuclease , rna , organic chemistry , electrical engineering , gene , engineering
The high structural resolution of the main transition states for the formation of native structure for the six small proteins of which Φ‐values for a large set of mutants have become available, barstar, barnase, chymotrypsin inhibitor 2, Arc repressor, the src SH3 domain, and a tetrameric p53 domain reveals that for the first 5 of these proteins: (1) Residues that belong to regular secondary structure have a significantly larger average fraction of native structural consolidation than residues in loops; (2) on the other hand, secondary and tertiary structures have built up to the same degree, or at least a high degree, but nonuniformly distributed over the molecule; (3) the most consolidated parts of each protein molecule in the transition state cluster together, and these clusters contain a significantly higher percentage of residues that belong to regular secondary structure than the rest of the molecule. These observations further reconcile the framework model with the nucleation‐condensation mechanism for folding: The amazing speed of protein folding can be understood as caused by the catalytic effect of the formation of clusters of residues which have particularly high preferences for the early formation of regular secondary structure in the presence of significant amounts of tertiary structure interactions. Proteins 2000;41:288–298. © 2000 Wiley‐Liss, Inc.