Structural basis for budding by the ESCRT-III factor CHMP3

Dev Cell. 2006 Jun;10(6):821-30. doi: 10.1016/j.devcel.2006.03.013.

Abstract

The vacuolar protein sorting machinery regulates multivesicular body biogenesis and is selectively recruited by enveloped viruses to support budding. Here we report the crystal structure of the human ESCRT-III protein CHMP3 at 2.8 A resolution. The core structure of CHMP3 folds into a flat helical arrangement that assembles into a lattice, mainly via two different dimerization modes, and unilaterally exposes a highly basic surface. The C terminus, the target for Vps4-induced ESCRT disassembly, extends from the opposite side of the membrane targeting region. Mutations within the basic and dimerization regions hinder bilayer interaction in vivo and reverse the dominant-negative effect of a truncated CHMP3 fusion protein on HIV-1 budding. Thus, the final steps in the budding process may include CHMP protein polymerization and lattice formation on membranes by employing different bilayer-recognizing surfaces, a function shared by all CHMP family members.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids, Acidic / chemistry
  • Amino Acids, Basic / chemistry
  • Conserved Sequence
  • Crystallography, X-Ray*
  • Dimerization
  • Endosomal Sorting Complexes Required for Transport
  • HIV Infections* / metabolism
  • HIV Infections* / virology
  • HIV-1 / physiology*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Protein Structure, Secondary
  • Protein Transport
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Static Electricity
  • Vesicular Transport Proteins / chemistry*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • Virus Replication

Substances

  • Amino Acids, Acidic
  • Amino Acids, Basic
  • CHMP3 protein, human
  • Endosomal Sorting Complexes Required for Transport
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • Vesicular Transport Proteins