Important role of hydrogen bonds in the structurally polarized transition state for folding of the src SH3 domain.
Experimental and theoretical studies on the folding of small proteins such as the chymotrypsin inhibitor 2 (CI-2) and the P22 Arc repressor suggest that the folding transition state is an expanded version of the native state with most interactions partially formed. Here we report that this picture does not hold generally: a hydrogen bond network involving two beta-turns and an adjacent hydrophobic cluster appear to be formed in the folding transition state of the src SH3 domain, while the remainder of the polypeptide chain is largely unstructured. Comparison with data on other small proteins suggests that this structural polarization is a consequence of the topology of the SH3 domain fold. The non-uniform distribution of structure in the folding transition state provides a challenging test for computational models of the folding process.
Department of Biochemistry, University of Washington, Seattle 98195, USA.
V P
VP
Grantcharova
D S
DS
Riddle
J V
JV
Santiago
D
D
Baker
D017022:Flow Injection Analysis; D019791:Guanidine / Q000494:pharmacology; D006860:Hydrogen Bonding; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D018909:src Homology Domains
D016392:Proto-Oncogene Proteins pp60(c-src); D019791:Guanidine