Understanding key features in transthyretin stability and their implications on therapeutic strategies

DOI

We propose to carry out a neutron structural study of human transthyretin (TTR) Thr119Met variant. This variant has been reported to have a protective role in the development of clinical symptoms in TTR amyloidosis patients. The neutron structure will help understand the inter-subunit contacts of TTR which contribute to the increase of protein stability, and possibly lead to the protective effect of the TTR variant. Such data will contribute greatly to the development of therapeutic strategies for TTR amyloidosis. This study is part of an extended series of measurements on a variety of mutants of wild-type TTR. In the previous allocation round, time on D19 was awarded for the study of another mutant (Ser52Pro) that has the opposite effect on TTR, and is known to enhance amyloidosis and fibrillogenesis. Hence a detailed comparison of the two structures with the wild type neutron structure will be of direct interest for an understanding of the factors underlying TTR stability. Detailed X-ray studies (both in crystals and solution) have already been carried out.

Identifier
DOI https://doi.org/10.5291/ILL-DATA.8-01-428
Metadata Access https://data.ill.fr/openaire/oai?verb=GetRecord&metadataPrefix=oai_datacite&identifier=10.5291/ILL-DATA.8-01-428
Provenance
Creator Yee, Ai Woon; Mitchell, Edward; Mossou, Estelle; Cooper, Jonathan; Blakeley, Matthew; Haertlein, Michael; Forsyth, Victor Trevor
Publisher Institut Laue-Langevin
Publication Year 2015
Rights OpenAccess; info:eu-repo/semantics/openAccess
OpenAccess true
Representation
Resource Type Dataset
Size 2 GB
Version 1
Discipline Particles, Nuclei and Fields