Crystal Structure of Metastasis-Associated Protein S100A4 in the Active Calcium-Bound Form

JOURNAL OF MOLECULAR BIOLOGY

卷:383

Article

Pathuri, Puja¹  Vogeley, Lutz¹  Luecke, Hartmut^1,2,3,4 

[1] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA

[3] Univ Calif Irvine, Dept Informat & Comp Sci, Irvine, CA 92697 USA

[4] Univ Calif Irvine, Ctr Biomembrane Syst, Irvine, CA 92697 USA

关键词: S100;    metastasis;    merohedral twinning;    angiogenesis;    calcium binding;   

DOI  :  10.1016/j.jmb.2008.04.076

来源: Elsevier

【 摘 要 】

S100A4 (metastasin) is a member of the S100 family of calcium-binding proteins that is directly involved in tumorigenesis. Until recently, the only structural information available was the solution NMR structure of the inactive calcium-free form of the protein. Here we report the crystal structure of human S100A4 in the active calcium-bound state at 2.03 angstrom resolution that was solved by molecular replacement in the space group P6(5) with two molecules in the asymmetric unit from perfectly merohedrally twinned crystals. The Ca2+-bound S100A4 structure reveals a large conformational change in the three-dimensional structure of the dimeric S100A4 protein upon calcium binding. This calcium-dependent conformational change opens up a hydrophobic binding pocket that is capable of binding to target proteins such as annexin A2, the tumor-suppressor protein p53 and myosin IIA. The structure of the active form of S100A4 provides insight into its interactions with its binding partners and a better understanding of its role in metastasis. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

Free