Identification of a key structural element for protein folding within beta-hairpin turns.


Specific residues in a polypeptide may be key contributors to the stability and foldability of the unique native structure. Identification and prediction of such residues is, therefore, an important area of investigation in solving the protein folding problem. Atypical main-chain conformations can help identify strains within a folded protein, and by inference, positions where unique amino acids may have a naturally high frequency of occurrence due to favorable contributions to stability and folding. Non-Gly residues located near the left-handed alpha-helical region (L-alpha) of the Ramachandran plot are a potential indicator of structural strain. Although many investigators have studied mutations at such positions, no consistent energetic or kinetic contributions to stability or folding have been elucidated. Here we report a study of the effects of Gly, Ala and Asn substitutions found within the L-alpha region at a characteristic position in defined beta-hairpin turns within human acidic fibroblast growth factor, and demonstrate consistent effects upon stability and folding kinetics. The thermodynamic and kinetic data are compared to available data for similar mutations in other proteins, with excellent agreement. The results have identified that Gly at the i+3 position within a subset of beta-hairpin turns is a key contributor towards increasing the rate of folding to the native state of the polypeptide while leaving the rate of unfolding largely unchanged. Study holds ProTherm entries: 16086, 16087, 16088, 16089, 16090, 16091, 16092, 16093 Extra Details: 2 mM DTT was added in the experiment beta-hairpin; fibroblast growth factor; folding kinetics; stability; trefoil

Submission Details

ID: k7ryDQke

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:47 p.m.

Version: 1

Publication Details
Kim J;Brych SR;Lee J;Logan TM;Blaber M,J. Mol. Biol. (2003) Identification of a key structural element for protein folding within beta-hairpin turns. PMID:12729767
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