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| [[Image:2q91.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2q91| PDB=2q91 | SCENE= }} | | {{STRUCTURE_2q91| PDB=2q91 | SCENE= }} |
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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=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_18410126}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18410126 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18410126}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Myosin]] | | [[Category: Myosin]] |
| [[Category: S100a4]] | | [[Category: S100a4]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 7 08:50:37 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:43:36 2008'' |