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ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes

DOI: 10.1073/pnas.1206839109 DOI Help
PMID: 23045692 PMID Help

Authors: Michael Hadders (Laboratory of Molecular Biology, Medical Research Council) , Monica Agromayor (King’s College London School of Medicine) , Takayuki Obita (Laboratory of Molecular Biology, Medical Research Council) , Olga Perisic (Laboratory of Molecular Biology, Medical Research Council) , Anna Caballe (King’s College London School of Medicine) , Magdalena Kloc (King’s College London School of Medicine) , Meindert H. Lamers (Laboratory of Molecular Biology, Medical Research Council) , Roger L. Williams (Laboratory of Molecular Biology, Medical Research Council) , Juan Martin-serrano (King’s College London School of Medicine)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 109 (43) , PAGES 17424 - 17429

State: Published (Approved)
Published: October 2012
Diamond Proposal Number(s): 8547

Abstract: The endosomal sorting complexes required for transport (ESCRT) proteins have a critical function in abscission, the final separation of the daughter cells during cytokinesis. Here, we describe the structure and function of a previously uncharacterized ESCRT-III interacting protein, MIT-domain containing protein 1 (MITD1). Crystal structures of MITD1 reveal a dimer, with a microtubule-interacting and trafficking (MIT) domain at the N terminus and a unique, unanticipated phospholipase D-like (PLD) domain at the C terminus that binds membranes. We show that the MIT domain binds to a subset of ESCRT-III subunits and that this interaction mediates MITD1 recruitment to the midbody during cytokinesis. Depletion of MITD1 causes a distinct cytokinetic phenotype consistent with destabilization of the midbody and abscission failure. These results suggest a model whereby MITD1 coordinates the activity of ESCRT-III during abscission with earlier events in the final stages of cell division.

Journal Keywords: X-Ray; Cytokinesis; Endosomal; HeLa; Humans; Membrane; Microtubule-Associated; Models; Molecular; Phospholipase; Protein; Protein Folding

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Other Facilities: no

Added On: 14/03/2013 09:36

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