Pathogenic Mutations Induce Partial Structural Changes in the Native β-Sheet Structure of Transthyretin and Accelerate Aggregation.

ABSTRACT: Amyloid formation of natively folded proteins involves global and/or local unfolding of the native state to form aggregation-prone intermediates. Here we report solid-state nuclear magnetic resonance (NMR) structural studies of amyloid derived from wild-type (WT) and more aggressive mutant forms of transthyretin (TTR) to investigate the structural changes associated with effective TTR aggregation. We employed selective ¹³C labeling schemes to investigate structural features of β-structured core regions in amyloid states of WT and two mutant forms (V30M and L55P) of TTR. Analyses of the ¹³C-¹³C correlation solid-state NMR spectra revealed that WT TTR aggregates contain an amyloid core consisting of nativelike CBEF and DAGH β-sheet structures, and the mutant

SUBMITTER: Lim KH 

PROVIDER: S-EPMC5745580 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature