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

Michael A. Hadders; Monica Agromayor; Takayuki Obita; Olga Perisic; Anna Caballe; Magdalena Kloc; Meindert H. Lamers; Roger L. Williams; Juan Martin-Serrano

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

机译：ESCRT-Ⅲ结合蛋白MITD1参与胞质分裂，并具有结合膜的意外PLD折叠

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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 destabiliza-tion 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.

机译：运输（ESCRT）蛋白所需的内体分选复合物在脱落，胞质分裂过程中子细胞的最终分离中起关键作用。在这里，我们描述了以前未知的ESCRT-Ⅲ相互作用蛋白，即含有MIT域的蛋白1（MITD1）的结构和功能。 MITD1的晶体结构揭示了一个二聚体，在N端具有一个微管相互作用和运输（MIT）域，在C端具有一个与膜结合的独特的，未预期的磷脂酶D样（PLD）域。我们表明，MIT结构域绑定到ESCRT-Ⅲ亚基的一个子集，并且这种相互作用在胞质分裂过程中介导MITD1募集到中体。 MITD1的消耗会导致明显的细胞动力学表型，与中体的不稳定和脱落失败相一致。这些结果提示了一个模型，其中MITD1协调脱落过程中ESCRT-Ⅲ的活性与细胞分裂最后阶段的早期事件。

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《Proceedings of the National Academy of Sciences of the United States of America》 |2012年第43期|17424-17429|共6页
作者
Michael A. Hadders; Monica Agromayor; Takayuki Obita; Olga Perisic; Anna Caballe; Magdalena Kloc; Meindert H. Lamers; Roger L. Williams; Juan Martin-Serrano;
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作者单位

Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 OQH, United Kingdom;

Department of Infectious Diseases, King's College London School of Medicine, London SE1 9RT, United Kingdom;

Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 OQH, United Kingdom;

Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 OQH, United Kingdom;

Department of Infectious Diseases, King's College London School of Medicine, London SE1 9RT, United Kingdom;

Department of Infectious Diseases, King's College London School of Medicine, London SE1 9RT, United Kingdom;

Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 OQH, United Kingdom;

Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 OQH, United Kingdom;

Department of Infectious Diseases, King's College London School of Medicine, London SE1 9RT, United Kingdom;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类
关键词
HIV; multivesicular body; X-ray crystallography;

机译：艾滋病病毒;多囊体X射线晶体学;

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6. ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes [O] . Michael A. Hadders, Monica Agromayor, Takayuki Obita, 2012

机译：ESCRT-III结合蛋白MITD1参与胞质分裂并具有结合膜的意外PLD折叠
7. ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes [O] . Hadders, Michael A., Agromayor, Monica, Obita, Takayuki, 2012

机译：ESCRT-III结合蛋白MITD1参与胞质分裂，并具有结合膜的意外PLD折叠

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

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