Conformational features of a peptide model Ac-DTVKLMYKGQPMTFR-NH2, corresponding to an early folding beta hairpin region of Staphylococcal nuclease

Abstract

Recent H-D exchange H-1 NMR studies of the refolding of Staphylococcal nuclease (P117G) variant suggest that, a region of the protein corresponding to a beta hairpin in the native structure folded early in the refolding process. In order to investigate whether the formation of beta hairpin is an early folding event, we investigated the conformational features of the beta hairpin peptide model Ac-DTVKLMYKGQPMTGR-NH2 from Staphylococcal nuclease with H-1 NMR techniques. Il. appears that the peptide aggregates even at a low concentration. However, based on the observation of weak dnn(i,i+1) NOEs between K8-G9, G9-Q10, an upfield shift of Gly9 NH and a low temperature coefficient (d delta/dT) for Gly9 NH, we suggest that the sequence YKGQP as part of the beta hairpin peptide model samples conformational forms with reduced conformational entropy and turn potential. The presence of aggregation could be restricting the population of folded conformational forms and formation of beta hairpin at detectable concentrations. We suggest that, formation of beta hairpin could be an early event in the folding of Staphylococcal nuclease and this observation correlates with H-D exchange H-1 NMR results and also with the prediction of a protein folding model proposed in literature.