Vps2

Vps2 is a protein component of the ESCRT-III complex that mediates membrane remodeling during the endosomal sorting pathway of eukaryotic cells. In Saccharomyces cerevisiae, VPS2 is one of several ESCRT-III subunits that drive the formation of intraluminal vesicles within multivesicular bodies. The protein is conserved across eukaryotes; in humans, the functional homologs are CHMP2A and CHMP2B.

Molecular function of Vps2 involves its participation in the late steps of intraluminal vesicle formation, polymerizing on endosomal membranes together with other ESCRT-III proteins such as Vps20 and Snf7 to shape membranes and promote scission. The C-terminal region contains a MIT-interacting motif that binds the MIT domain of the Vps4 ATPase. Vps4 drives disassembly and recycling of ESCRT-III components after membrane scission, a process essential for turnover of the complex. Vps2 activity is regulated by autoinhibitory interactions that keep it inactive until recruited to endosomal membranes.

Localization and regulation: Vps2 is predominantly cytosolic when inactive and is recruited to endosomes via interactions with other ESCRT-III subunits. Its activity is tightly regulated by autoinhibition through its C-terminus, and disassembly by Vps4 controls the dynamic turnover of ESCRT-III assemblies.

Clinical and research significance: Alterations in VPS2 or its human homologs, and disruptions to ESCRT-III function, have been studied in the context of human diseases including neurodegenerative disorders and cancer, reflecting roles in membrane trafficking, protein quality control, and viral budding.