Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B

Nat Struct Mol Biol. 2008 Dec;15(12):1278-86. doi: 10.1038/nsmb.1512. Epub 2008 Nov 9.


The endosomal sorting complex required for transport (ESCRT) machinery, including ESCRT-III, localizes to the midbody and participates in the membrane-abscission step of cytokinesis. The ESCRT-III protein charged multivesicular body protein 1B (CHMP1B) is required for recruitment of the MIT domain-containing protein spastin, a microtubule-severing enzyme, to the midbody. The 2.5-A structure of the C-terminal tail of CHMP1B with the MIT domain of spastin reveals a specific, high-affinity complex involving a noncanonical binding site between the first and third helices of the MIT domain. The structural interface is twice as large as that of the MIT domain of the VPS4-CHMP complex, consistent with the high affinity of the interaction. A series of unique hydrogen-bonding interactions and close packing of small side chains discriminate against the other ten human ESCRT-III subunits. Point mutants in the CHMP1B binding site of spastin block recruitment of spastin to the midbody and impair cytokinesis.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism*
  • Binding Sites
  • Codon, Nonsense
  • Crystallography, X-Ray
  • Endosomal Sorting Complexes Required for Transport
  • HeLa Cells
  • Humans
  • Microscopy, Confocal
  • Models, Biological
  • Models, Molecular
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Spastin
  • Two-Hybrid System Techniques
  • Vesicular Transport Proteins


  • CHMP1A protein, human
  • CHMP1B protein, human
  • Codon, Nonsense
  • Endosomal Sorting Complexes Required for Transport
  • Nuclear Proteins
  • Vesicular Transport Proteins
  • Adenosine Triphosphatases
  • Spastin
  • SPAST protein, human