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Structure determination of transthyretin amyloid fibrils extracted from amyloidosis patients


EMSL Project ID
51267

Abstract

Here, we aim to use cryo-electron microscopy to determine the structures of full-length transthyretin fibrils extracted from autopsied or explanted hearts from ATTR patients carrying either a wild-type form of transthyretin or familial mutants. We hypothesize that the phenotypical variation found in ATTR patients may be explained by structural polymorphism. We will compare the structure of the ex-vivo fibrils extracted from at least five different genotypes, with the hope to shed light on the mechanism of transthyretin misfolding and to open new avenues for developing therapeutic inhibitors for both wild-type and hereditary ATTR. Using structure-based design, the new structures will enable us to design a new generation of peptide inhibitors that have the potential to block transthyretin aggregation.

Project Details

Start Date
2020-02-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Lorena Saelices
Institution
University of Texas Southwestern Medical Center

Co-Investigator(s)

David Eisenberg
Institution
University of California, Los Angeles

Team Members

Binh Nguyen
Institution
University of Texas Southwestern Medical Center

Harry Scott
Institution
Oregon Health & Science University

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory