| Structural highlights
Function
CIB1_HUMAN May convert the inactive conformation of integrin alpha-IIb/beta3 to an active form through binding to the integrin cytoplasmic domain. Induces cell migration and spreading mediated through integrin (possibly via focal adhesion complexes). Functions as a negative regulator of stress activated MAP kinase (MAPK) signaling pathways. May play a role in regulation of apoptosis. Interacts with and up-regulates PTK2/FAK1 activity. Down regulates inositol 1,4,5-trisphosphate receptor-dependent calcium signaling. Participates in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Calcium and integrin binding protein 1 (CIB1) is a specific binding partner for the cytoplasmic domain of the alphaIIb subunit of the highly abundant platelet integrin alphaIIbbeta3. This protein has been suggested to be involved in the regulation of the activation of alphaIIbbeta3, a process leading to platelet aggregation and blood coagulation. In this work, the solution structure of the deuterated Ca(2+)-CIB1 protein complexed with an alphaIIb peptide was first determined through modern RDC-based NMR methods. Next, we generated a complex structure for CIB1 and the alphaIIb domain (Ca(2+)-CIB1/alphaIIb) using the program Haddock, which is based on experimental restraints obtained for the protein-peptide interface from cross-saturation NMR experiments. In this data-driven complex structure, the N-terminal alpha-helix of the cytoplasmic domain of alphaIIb is buried in the hydrophobic pocket of the C-lobe of Ca(2+)-CIB1. The C-terminal acidic tail of alphaIIb remains unstructured and likely interacts with several positively charged residues in the N-lobe of Ca(2+)-CIB1. A potential molecular mechanism for the CIB1-mediated activation of the platelet integrin could be proposed on the basis of the model structure of this protein complex. Another feature of this work is that, in the NMR cross-saturation experiments, we applied the selective radio frequency irradiation to the smaller binding partner (the alphaIIb peptide), and successfully detected the binding interface on the larger binding partner Ca(2+)-CIB1 through its selectively protonated methyl groups. This 'reverse' methodology has a broad potential to be employed to many other complexes where synthetic peptides and a suitably isotope-labeled medium- to large-sized protein are used to study protein-protein interactions.
Structural basis for the activation of platelet integrin alphaIIbbeta3 by calcium- and integrin-binding protein 1.,Huang H, Vogel HJ J Am Chem Soc. 2012 Feb 29;134(8):3864-72. doi: 10.1021/ja2111306. Epub 2012 Feb , 16. PMID:22283712[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Naik UP, Naik MU. Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen. Blood. 2003 Aug 15;102(4):1355-62. Epub 2003 Apr 24. PMID:12714504 doi:10.1182/blood-2003-02-0591
- ↑ Naik MU, Naik UP. Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen. Blood. 2003 Nov 15;102(10):3629-36. Epub 2003 Jul 24. PMID:12881299 doi:10.1182/blood-2003-05-1703
- ↑ Tahara E Jr, Tahara H, Kanno M, Naka K, Takeda Y, Matsuzaki T, Yamazaki R, Ishihara H, Yasui W, Barrett JC, Ide T, Tahara E. G1P3, an interferon inducible gene 6-16, is expressed in gastric cancers and inhibits mitochondrial-mediated apoptosis in gastric cancer cell line TMK-1 cell. Cancer Immunol Immunother. 2005 Aug;54(8):729-40. Epub 2005 Feb 1. PMID:15685448 doi:10.1007/s00262-004-0645-2
- ↑ Hennigs JK, Burhenne N, Stahler F, Winnig M, Walter B, Meyerhof W, Schmale H. Sweet taste receptor interacting protein CIB1 is a general inhibitor of InsP3-dependent Ca2+ release in vivo. J Neurochem. 2008 Sep;106(5):2249-62. doi: 10.1111/j.1471-4159.2008.05563.x. PMID:18627437 doi:10.1111/j.1471-4159.2008.05563.x
- ↑ Yoon KW, Cho JH, Lee JK, Kang YH, Chae JS, Kim YM, Kim J, Kim EK, Kim SE, Baik JH, Naik UP, Cho SG, Choi EJ. CIB1 functions as a Ca(2+)-sensitive modulator of stress-induced signaling by targeting ASK1. Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17389-94. doi:, 10.1073/pnas.0812259106. Epub 2009 Sep 29. PMID:19805025 doi:10.1073/pnas.0812259106
- ↑ Kostyak JC, Naik UP. Calcium- and integrin-binding protein 1 regulates endomitosis and its interaction with Polo-like kinase 3 is enhanced in endomitotic Dami cells. PLoS One. 2011 Jan 14;6(1):e14513. doi: 10.1371/journal.pone.0014513. PMID:21264284 doi:10.1371/journal.pone.0014513
- ↑ Huang H, Vogel HJ. Structural basis for the activation of platelet integrin alphaIIbbeta3 by calcium- and integrin-binding protein 1. J Am Chem Soc. 2012 Feb 29;134(8):3864-72. doi: 10.1021/ja2111306. Epub 2012 Feb , 16. PMID:22283712 doi:10.1021/ja2111306
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