Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B.
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.
Yang
Dong
D
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Rismanchi
Neggy
N
Renvoisé
Benoît
B
Lippincott-Schwartz
Jennifer
J
Blackstone
Craig
C
Hurley
James H
JH
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018389:Codon, Nonsense; D018360:Crystallography, X-Ray; D056827:Endosomal Sorting Complexes Required for Transport; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D008954:Models, Biological; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D000074181:Spastin; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins
C443709:CHMP1A protein, human; C541483:CHMP1B protein, human; D018389:Codon, Nonsense; D056827:Endosomal Sorting Complexes Required for Transport; D009687:Nuclear Proteins; D033921:Vesicular Transport Proteins; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human