2q91

Structure of the Ca2+-Bound Activated Form of the S100A4 Metastasis Factor

spinqualitylabelsall models 2q91, resolution 1.63Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2q91 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Gene: S100A4, CAPL, MTS1 (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed S100A4, also known as mts1, is a member of the S100 family of Ca (2+)-binding proteins that is directly involved in tumor invasion and metastasis via interactions with specific protein targets, including nonmuscle myosin-IIA (MIIA). Human S100A4 binds two Ca (2+) ions with the typical EF-hand exhibiting an affinity that is nearly 1 order of magnitude tighter than that of the pseudo-EF-hand. To examine how Ca (2+) modifies the overall organization and structure of the protein, we determined the 1.7 A crystal structure of the human Ca (2+)-S100A4. Ca (2+) binding induces a large reorientation of helix 3 in the typical EF-hand. This reorganization exposes a hydrophobic cleft that is comprised of residues from the hinge region, helix 3, and helix 4, which afford specific target recognition and binding. The Ca (2+)-dependent conformational change is required for S100A4 to bind peptide sequences derived from the C-terminal portion of the MIIA rod with submicromolar affinity. In addition, the level of binding of Ca (2+) to both EF-hands increases by 1 order of magnitude in the presence of MIIA. NMR spectroscopy studies demonstrate that following titration with a MIIA peptide, the largest chemical shift perturbations and exchange broadening effects occur for residues in the hydrophobic pocket of Ca (2+)-S100A4. Most of these residues are not exposed in apo-S100A4 and explain the Ca (2+) dependence of formation of the S100A4-MIIA complex. These studies provide the foundation for understanding S100A4 target recognition and may support the development of reagents that interfere with S100A4 function. Structure of Ca(2+)-Bound S100A4 and Its Interaction with Peptides Derived from Nonmuscle Myosin-IIA.,Malashkevich VN, Varney KM, Garrett SC, Wilder PT, Knight D, Charpentier TH, Ramagopal UA, Almo SC, Weber DJ, Bresnick AR Biochemistry. 2008 May 6;47(18):5111-5126. Epub 2008 Apr 15. PMID:18410126 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also S100 protein

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