| 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
The Calcium and Integrin Binding protein 1 (CIB1) is a ubiquitous Ca(2+) binding protein and a specific binding partner for the platelet integrin alphaIIb cytoplasmic domain, which confers CIB1's key role in haemostasis. CIB1 is also known to be involved in apoptosis, embryogenesis and the DNA damage response. In this work, the solution structures of both Ca(2+)-CIB1 and Mg(2+)-CIB1 were determined using solution-state NMR spectroscopy. The methyl groups of Ile,Leu and Val were selectively protonated to compensate for the loss of protons due to deuteration. The solution structure of Ca(2+)-CIB1 possesses smaller opened EF-hands in its C-domain compared to available crystal structures. Ca(2+)-CIB1 and Mg(2+)-CIB1 have similar structures, but the N-lobe of Mg(2+)-CIB1 is slightly more opened than that of Ca(2+)-CIB1. Additional NMR experiments, such as chemical shift perturbation and methyl group solvent accessibility as measured by the surface probe TEMPOL were carried out to further characterize the structures of Ca(2+)-CIB1 and Mg(2+)-CIB1 as well as their interactions with the integrin alphaIIb cytoplasmic domain. NMR measurements of backbone amide proton slow motion (mus-ms) dynamics confirmed that the C-terminal helix of Ca(2+)-CIB1 is displaced upon alphaIIb binding. The EF-hand III of both Ca(2+)-CIB1 and Mg(2+)-CIB1 was identified to be directly involved in the interaction of CIB1 and alphaIIb. Together, these data illustrate that CIB1 behaves quite different from related EF-hand regulatory calcium-binding proteins, such as calmodulin or neuronal calcium sensor proteins.
The solution structures of Ca2+- CIB1 and Mg2+-CIB1 and their interactions with the platelet integrin {alpha}IIb cytoplasmic domain.,Huang H, Ishida H, Yamniuk AP, Vogel HJ J Biol Chem. 2011 Mar 9. PMID:21388953[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, Ishida H, Yamniuk AP, Vogel HJ. The solution structures of Ca2+- CIB1 and Mg2+-CIB1 and their interactions with the platelet integrin {alpha}IIb cytoplasmic domain. J Biol Chem. 2011 Mar 9. PMID:21388953 doi:10.1074/jbc.M110.179028
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