In silico modeling human VPS13 proteins associated with donor and target membranes suggests lipid transfer mechanisms.

ABSTRACT: The VPS13 protein family constitutes a novel class of bridge-like lipid transferases. Autosomal recessive inheritance of mutations in VPS13 genes is associated with the development of neurodegenerative diseases in humans. Bioinformatic approaches previously recognized the domain architecture of these proteins. In this study, we model the first ever full-length structures of the four human homologs VPS13A, VPS13B, VPS13C, and VPS13D in association with model membranes, to investigate their lipid transfer ability and potential structural association with membrane leaflets. We analyze the evolutionary conservation and physicochemical properties of these proteins, focusing on conserved C-terminal amphipathic helices that disturb organelle surfaces and that, adjoined, resemble a traditional Ven

SUBMITTER: Dall'Armellina F 

PROVIDER: S-EPMC10953354 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature