Cryo-EM structure of amyloid fibrils formed by full-length human αA-crystallin with pathogenic mutation R116C.

ABSTRACT: The aggregation of crystallin proteins in human lens is the primary cause of cataracts, a disease that leads to blindness of tens of millions of people worldwide. Understanding the molecular architectures of these aggregated crystallin proteins can facilitate the development of therapeutic drugs to treat cataract without surgery. In this study, we prepared two types of crystallin fibrils, thick and thin, using recombinant human αA-crystallin harboring the disease-associated R116C mutation under neutral and acidic conditions, respectively. The structure of the thin fibrils was determined via cryo-EM at a resolution of 3.7 Å, whereas the thick fibrils appeared unsuitable for cryo-EM structure determination. Structure analysis suggests that the thin fibrils adopt a three-layered structure sta

SUBMITTER: Song M 

PROVIDER: S-EPMC12329027 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature