2q91: Difference between revisions
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'''Structure of the Ca2+-Bound Activated Form of the S100A4 Metastasis Factor''' | '''Structure of the Ca2+-Bound Activated Form of the S100A4 Metastasis Factor''' | ||
==Overview== | |||
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. | |||
==About this Structure== | ==About this Structure== | ||
2Q91 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q91 OCA]. | 2Q91 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q91 OCA]. | ||
==Reference== | |||
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:[http://www.ncbi.nlm.nih.gov/pubmed/18410126 18410126] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Myosin]] | [[Category: Myosin]] | ||
[[Category: S100a4]] | [[Category: S100a4]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 7 08:50:37 2008'' | ||