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Structure/Function Analysis of Four Core ESCRT‐III Proteins Reveals Common Regulatory Role for Extreme C‐Terminal Domain
Author(s) -
Shim Soomin,
Kimpler Lisa A.,
Hanson Phyllis I.
Publication year - 2007
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2007.00584.x
Subject(s) - escrt , endosome , biology , biogenesis , microbiology and biotechnology , c terminus , transport protein , n terminus , vesicular transport proteins , function (biology) , amino acid , vacuolar protein sorting , peptide sequence , biochemistry , gene , intracellular
Endosomal sorting complex required for transport‐III (ESCRT‐III) is a large complex built from related ESCRT‐III proteins involved in multivesicular body biogenesis. Little is known about the structure and function of this complex. Here, we compare four human ESCRT‐III proteins – hVps2‐1/CHMP2a, hVps24/CHMP3, hVps20/CHMP6, and hSnf7‐1/CHMP4a – to each other, studying the effects of deleting predicted α‐helical domains on their behavior in transfected cells. Surprisingly, removing ∼40 amino acids from the C‐terminus of each protein unmasks a common ability to associate with endosomal membranes and assemble into large polymeric complexes. Expressing these truncated ESCRT‐III proteins in cultured cells causes ubiquitinated cargo to accumulate on enlarged endosomes and inhibits viral budding, while expressing full‐length proteins does not. hVps2‐1/CHMP2a lacking its C‐terminal 42 amino acids further fails to bind to the AAA+ adenosine triphosphatase VPS4B/SKD1, indicating that C‐terminal sequences are important for interaction of ESCRT‐III proteins with VPS4. Overall, our study supports a model in which ESCRT‐III proteins cycle between a default ‘closed’ state and an activated ‘open’ state under control of sequences at their C‐terminus and associated factors.