Probing Medin Monomer Structure and its Amyloid Nucleation Using ¹³C-Direct Detection NMR in Combination with Structural Bioinformatics.

ABSTRACT: Aortic medial amyloid is the most prevalent amyloid found to date, but remarkably little is known about it. It is characterised by aberrant deposition of a 5.4 kDa protein called medin within the medial layer of large arteries. Here we employ a combined approach of ab initio protein modelling and ¹³C-direct detection NMR to generate a model for soluble monomeric medin comprising a stable core of three β-strands and shorter more labile strands at the termini. Molecular dynamics simulations suggested that detachment of the short, C-terminal β-strand from the soluble fold exposes key amyloidogenic regions as a potential site of nucleation enabling dimerisation and subsequent fibril formation. This mechanism resembles models proposed for several other amyloidogenic proteins suggesti

SUBMITTER: Davies HA 

PROVIDER: S-EPMC5361114 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature