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J. Biol. Chem., Vol. 282, Issue 1, 647-656, January 5, 2007

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Structure of Human Spindlin1

TANDEM TUDOR-LIKE DOMAINS FOR CELL CYCLE REGULATION^*

Qiang Zhao¹, Lipeng Qin¹, Fuguo Jiang, Beili Wu, Wen Yue, Feng Xu, Zhili Rong^¶, Hongfeng Yuan, Xiaoyan Xie, Yanhong Gao, Cixian Bai, Mark Bartlam, Xuetao Pei², and Zihe Rao³

From the Tsinghua-Institute of Biophysics Joint Research Group for Structural Biology, Tsinghua University, Beijing 100084, China and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, Department of Stem Cell Biology, Beijing Institute of Transfusion Medicine, Beijing 100850, China, and ^¶Tsinghua Institute of Genome Research, School of Medicine, Tsinghua University, Beijing 100084, China

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 2.2Å 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 -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.

Received for publication, April 27, 2006 , and in revised form, November 1, 2006.

The atomic coordinates and structure factors (code 2NS2) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This study was supported by Ministry of Science and Technology Human Liver Proteomics Project Grant 2004CB520801, State 863 High-Tech Project Grants 2002BA711A12 and 2002AA205050 and 973 Project Grants G1999075602 and 2001CB509906, and the National Natural Science Foundation of China Grants 30221003 and 30271359. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These authors made equal contributions.

² To whom correspondence may be addressed. E-mail: peixt{at}nic.bmi.ac.cn.

³ To whom correspondence may be addressed. E-mail: raozh{at}xtal.tsinghua.edu.cn.

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