Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex

Dev Cell. 2008 Jun;14(6):902-13. doi: 10.1016/j.devcel.2008.04.004.


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


  • 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

Associated data

  • PDB/2ZME
  • PDB/3CUQ