Peptide Model of the Mutant Proinsulin Syndrome. II. Nascent Structure and Biological Implications.

ABSTRACT: Toxic misfolding of proinsulin variants in β-cells defines a monogenic diabetes syndrome, designated mutant INS-gene induced diabetes of the young (MIDY). In our first study (previous article in this issue), we described a one-disulfide peptide model of a proinsulin folding intermediate and its use to study such variants. The mutations (Leu^B15→Pro, Leu^A16→Pro, and Phe^B24→Ser) probe residues conserved among vertebrate insulins. In this companion study, we describe ¹H and ¹H-¹³C NMR studies of the peptides; key NMR resonance assignments were verified by synthetic ¹³C-labeling. Parent spectra retain nativelike features in the neighborhood of the single disulfide bridge (cystine B19-A20), including secondary NM

SUBMITTER: Yang Y 

PROVIDER: S-EPMC8922542 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature