Observation of pH-Dependent Residual Structure in the Pmel17 Repeat Domain and the Implication for Its Amyloid Formation.

ABSTRACT: The varying conformational states of amyloid-forming protein monomers can determine their fibrillation outcome. In this study, we utilize solution NMR and the paramagnetic relaxation enhancement (PRE) effect to observe monomer properties of the repeat domain (RPT) from a human functional amyloid, premelanosomal protein, Pmel17. After excision from the full-length protein, RPT can self-assemble into amyloid fibrils, functioning as a scaffold for melanin deposition. Here, we report possible conformational states of the short RPT (sRPT) isoform, which has been demonstrated to be a fibrillation nucleator. NMR experiments were performed to determine conformational differences in sRPT by comparing aggregation-prone vs nonaggregating solution conditions. We observed significant chemical shift per

SUBMITTER: Morris DL 

PROVIDER: S-EPMC11822675 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature