Abstract
ESCRT-II plays a pivotal role in receptor downregulation and multivesicular body biogenesis and is conserved from yeast to humans. The crystal structures of two human ESCRT-II complex structures have been determined at 2.6 and 2.9 A resolution, respectively. The complex has three lobes and contains one copy each of VPS22 and VPS36 and two copies of VPS25. The structure reveals a dynamic helical domain to which both the VPS22 and VPS36 subunits contribute that connects the GLUE domain to the rest of the ESCRT-II core. Hydrodynamic analysis shows that intact ESCRT-II has a compact, closed conformation. ESCRT-II binds to the ESCRT-I VPS28 C-terminal domain subunit through a helix immediately C-terminal to the VPS36-GLUE domain. ESCRT-II is targeted to endosomal membranes by the lipid-binding activities of both the Vps36 GLUE domain and the first helix of Vps22. These data provide a unifying structural and functional framework for the ESCRT-II complex.
Publication types
-
Research Support, N.I.H., Intramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Amino Acid Motifs
-
Amino Acid Sequence
-
Binding Sites
-
Crystallography, X-Ray
-
Endosomal Sorting Complexes Required for Transport
-
Endosomes / chemistry*
-
Endosomes / metabolism
-
Glutathione Transferase / metabolism
-
Green Fluorescent Proteins / metabolism
-
Humans
-
Liposomes / metabolism
-
Membrane Proteins / chemistry*
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism
-
Models, Molecular
-
Models, Structural*
-
Molecular Sequence Data
-
Protein Binding / genetics
-
Protein Conformation
-
Protein Structure, Secondary
-
Protein Structure, Tertiary
-
Protein Subunits / chemistry
-
Protein Subunits / genetics
-
Protein Subunits / metabolism
-
Protein Transport / physiology*
-
Proteins / chemistry
-
Proteins / genetics
-
Proteins / metabolism
-
Saccharomyces cerevisiae / genetics
-
Saccharomyces cerevisiae Proteins / chemistry
-
Sequence Homology, Amino Acid
-
Vesicular Transport Proteins
Substances
-
Endosomal Sorting Complexes Required for Transport
-
Liposomes
-
Membrane Proteins
-
Protein Subunits
-
Proteins
-
SNF8 protein, human
-
Saccharomyces cerevisiae Proteins
-
Vesicular Transport Proteins
-
Green Fluorescent Proteins
-
Glutathione Transferase