Crystal structure of metastasis-associated protein S100A4 in the active calcium-bound form.
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 A 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 Ca(2+)-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.
Pathuri
Puja
P
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Vogeley
Lutz
L
Luecke
Hartmut
H
D000595:Amino Acid Sequence; D017306:Annexin A2 / Q000378:metabolism; D001059:Apoproteins / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
C472822:ANXA2 protein, human; D017306:Annexin A2; D001059:Apoproteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D002118:Calcium
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