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Published online before print September 30, 2004, 10.1110/ps.04937304
Protein Science (2004), 13:2845-2851. Published by Cold Spring Harbor Laboratory Press. Copyright © 2004 The Protein Society
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Crystal structure of human coactosin-like protein at 1.9 Å resolution

Xuemei Li1, Xueqi Liu2, Zhiyong Lou2, Xin Duan2, Hao Wu2, Yiwei Liu2 and Zihe Rao1,2

1 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China
2 Laboratory of Structural Biology, Tsinghua University, Beijing 100084, People’s Republic of China

(RECEIVED June 17, 2004; FINAL REVISION August 2, 2004; ACCEPTED August 5, 2004)

Human coactosin-like protein (CLP) shares high homology with coactosin, a filamentous (F)-actin binding protein, and interacts with 5LO and F-actin. As a tumor antigen, CLP is overexpressed in tumor tissue cells or cell lines, and the encoded epitopes can be recognized by cellular and humoral immune systems. To gain a better understanding of its various functions and interactions with related proteins, the crystal structure of CLP expressed in Escherichia coli has been determined to 1.9 Å resolution. The structure features a central {beta}-sheet surrounded by helices, with two very tight hydrophobic cores on each side of the sheet. CLP belongs to the actin depolymerizing protein superfamily, and is similar to yeast cofilin and actophilin. Based on our structural analysis, we observed that CLP forms a polymer along the crystallographic b axis with the exact same repeat distance as F-actin. A model for the CLP polymer and F-actin binding has therefore been proposed.

Keywords: coactosin-like protein; crystal structure; F-actin binding protein; tumor antigen; actin depolymerizing protein; polymer


Reprint requests to: Yiwei Liu or Zihe Rao, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China; e-mail: liuyw{at}xtal.tsinghua.edu.cn or raozh{at}xtal.tsinghua.edu.cn; fax: +86-10-62773145 or +86-10-64867566.


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