title: Structure of human spindlin1. Tandem tudor-like domains for cell cycle regulation.
abstract: Spindlin1, a meiotic spindle-binding protein that is highly expressed in ovarian cancer cells, was first identified as a gene involved in gametogenesis. It appeared to be a target for cell cycle-dependent phosphorylation and was demonstrated to disturb the cell cycle. Here we report the crystal structure of human spindlin1 to 2.2A of resolution, representing the first three-dimensional structure from the spin/ssty (Y-linked spermiogenesis-specific transcript) gene family. The refined structure, containing three repeats of five/four anti-parallel beta-strands, exhibits a novel arrangement of tandem Tudor-like domains. Two phosphate ions, chelated by Thr-95 and other residues, appear to stabilize the long loop between domains I and II, which might mediate the cell cycle regulation activity of spindlin1. Flow cytometry experiments indicate that cells expressing spindlin1 display a different cell cycle distribution in mitosis, whereas those expressing a T95A mutant, which had a great decrease in phosphorous content, have little effect on the cell cycle. We further identified associations of spindlin1 with nucleic acid to provide a biochemical basis for its cell cycle regulation and other functions.
authors.affiliation: Tsinghua-Institute of Biophysics Joint Research Group for Structural Biology, Tsinghua University, Beijing 100084, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: Lipeng
authors.initials: L
authors.lastname: Qin
authors.forename: Fuguo
authors.initials: F
authors.lastname: Jiang
authors.forename: Beili
authors.initials: B
authors.lastname: Wu
authors.forename: Wen
authors.initials: W
authors.lastname: Yue
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Zhili
authors.initials: Z
authors.lastname: Rong
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Yuan
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xie
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gao
authors.forename: Cixian
authors.initials: C
authors.lastname: Bai
authors.forename: Mark
authors.initials: M
authors.lastname: Bartlam
authors.forename: Xuetao
authors.initials: X
authors.lastname: Pei
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D007477:Ions; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010710:Phosphates / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013912:Threonine / Q000737:chemistry
chemical_list: D018797:Cell Cycle Proteins; D002614:Chelating Agents; D007477:Ions; D008869:Microtubule-Associated Proteins; D010710:Phosphates; D010750:Phosphoproteins; C104434:spindlin; D013912:Threonine