Structure of human spindlin1. Tandem tudor-like domains for cell cycle regulation.
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.
Zhao
Qiang
Q
Tsinghua-Institute of Biophysics Joint Research Group for Structural Biology, Tsinghua University, Beijing 100084, China.
Qin
Lipeng
L
Jiang
Fuguo
F
Wu
Beili
B
Yue
Wen
W
Xu
Feng
F
Rong
Zhili
Z
Yuan
Hongfeng
H
Xie
Xiaoyan
X
Gao
Yanhong
Y
Bai
Cixian
C
Bartlam
Mark
M
Pei
Xuetao
X
Rao
Zihe
Z
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
D018797:Cell Cycle Proteins; D002614:Chelating Agents; D007477:Ions; D008869:Microtubule-Associated Proteins; D010710:Phosphates; D010750:Phosphoproteins; C104434:spindlin; D013912:Threonine