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
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Fibroblast growth factor 1 P05230 FGF1_HUMAN
100.0 Fibroblast growth factor 1 Q5NVQ3 FGF1_PONAB
97.9 Fibroblast growth factor 1 P34004 FGF1_MESAU
98.0 Fibroblast growth factor 1 P20002 FGF1_PIG
96.4 Fibroblast growth factor 1 P61148 FGF1_MOUSE
96.4 Fibroblast growth factor 1 P61149 FGF1_RAT
92.3 Fibroblast growth factor 1 P03968 FGF1_BOVIN
90.7 Fibroblast growth factor 1 Q7M303 FGF1_SHEEP
90.3 Fibroblast growth factor 1 P19596 FGF1_CHICK
91.5 Fibroblast growth factor 1 Q9N1S8 FGF1_CAPCA