Cataract-prone variants of γD-crystallin populate a conformation with a partially unfolded N-terminal domain under native conditions.

ABSTRACT: Human γD-crystallin, a monomeric protein abundant in the eye lens nucleus, must remain stably folded for an individual's entire lifetime to avoid aggregation and protein deposition-associated cataract formation. γD-crystallin contains two homologous domains, an N-terminal domain (NTD) and a C-terminal domain (CTD), which interact via a hydrophobic interface. Several familial mutations in the gamma crystallin gene are linked to congenital early-onset cataract, most of which affect the NTD. Some of these, including V75D and W42R, are known to populate intermediates under partially denaturing conditions possessing a natively folded CTD and a completely unfolded NTD. We employed hydrogen-deuterium exchange mass spectrometry to probe the structural and energetic features of variants of γD-cryst

SUBMITTER: Volz S 

PROVIDER: S-EPMC11831119 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature