title: Mechanistic insights into the anchorage of the contractile ring by anillin and Mid1.
abstract: Anillins and Mid1 are scaffold proteins that play key roles in anchorage of the contractile ring at the cell equator during cytokinesis in animals and fungi, respectively. Here, we report crystal structures and functional analysis of human anillin and S. pombe Mid1. The combined data show anillin contains a cryptic C2 domain and a Rho-binding domain. Together with the tethering PH domain, three membrane-associating elements synergistically bind to RhoA and phospholipids to anchor anillin at the cleavage furrow. Surprisingly, Mid1 also binds to the membrane through a cryptic C2 domain. Dimerization of Mid1 leads to high affinity and preference for PI(4,5)P2, which stably anchors Mid1 at the division plane, bypassing the requirement for Rho GTPase. These findings uncover the unexpected general machinery and the divergent regulatory logics for the anchorage of the contractile ring through the anillin/Mid1 family proteins from yeast to humans.
authors.affiliation: MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Science, Tsinghua University, Beijing 100084, China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Sun
authors.affiliation: MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Science, Tsinghua University, Beijing 100084, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Guan
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: I-Ju
authors.initials: IJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Science, Tsinghua University, Beijing 100084, China.
authors.forename: Mengran
authors.initials: M
authors.lastname: Chen
authors.affiliation: School of Life Science, Tsinghua University, Beijing 100084, China; State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jian-Qiu
authors.initials: JQ
authors.lastname: Wu
authors.affiliation: MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Science, Tsinghua University, Beijing 100084, China. Electronic address: zhucheng_chen@tsinghua.edu.cn.
authors.forename: Zhucheng
authors.initials: Z
authors.lastname: Chen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D018360:Crystallography, X-Ray; D048749:Cytokinesis / Q000502:physiology; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: C000591059:ANLN protein, human; D008840:Microfilament Proteins; C489694:Mid1 protein, S pombe; D010743:Phospholipids; D029702:Schizosaccharomyces pombe Proteins; D020742:rhoA GTP-Binding Protein