Structural highlights
Function
[AIF1_HUMAN] Actin-binding protein that enhances membrane ruffling and RAC activation. Enhances the actin-bundling activity of LCP1. Binds calcium. Plays a role in RAC signaling and in phagocytosis. May play a role in macrophage activation and function. Promotes the proliferation of vascular smooth muscle cells and of T-lymphocytes. Enhances lymphocyte migration. Plays a role in vascular inflammation.[1] [2] [3]
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
The ionized calcium-binding adaptor molecule 1 (Iba1) with 147 amino acid residues has been identified as a calcium-binding protein, expressed specifically in microglia/macrophages, and is expected to be a key factor in membrane ruffling, which is a typical feature of activated microglia. We have determined the crystal structure of human Iba1 in a Ca(2+)-free form and mouse Iba1 in a Ca(2+)-bound form, to a resolution of 1.9 A and 2.1 A, respectively. X-ray structures of Iba1 revealed a compact, single-domain protein with two EF-hand motifs, showing similarity in overall topology to partial structures of the classical EF-hand proteins troponin C and calmodulin. In mouse Iba1, the second EF-hand contains a bound Ca(2+), but the first EF-hand does not, which is often the case in S100 proteins, suggesting that Iba1 has S100 protein-like EF-hands. The molecular conformational change induced by Ca(2+)-binding of Iba1 is different from that found in the classical EF-hand proteins and/or S100 proteins, which demonstrates that Iba1 has an unique molecular switching mechanism dependent on Ca(2+)-binding, to interact with target molecules.
X-ray structures of the microglia/macrophage-specific protein Iba1 from human and mouse demonstrate novel molecular conformation change induced by calcium binding.,Yamada M, Ohsawa K, Imai Y, Kohsaka S, Kamitori S J Mol Biol. 2006 Dec 1;364(3):449-57. Epub 2006 Sep 15. PMID:17011575[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chen X, Kelemen SE, Autieri MV. AIF-1 expression modulates proliferation of human vascular smooth muscle cells by autocrine expression of G-CSF. Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1217-22. Epub 2004 Apr 29. PMID:15117732 doi:http://dx.doi.org/10.1161/01.ATV.0000130024.50058.de
- ↑ Kelemen SE, Autieri MV. Expression of allograft inflammatory factor-1 in T lymphocytes: a role in T-lymphocyte activation and proliferative arteriopathies. Am J Pathol. 2005 Aug;167(2):619-26. PMID:16049345 doi:http://dx.doi.org/10.1016/S0002-9440(10)63003-9
- ↑ Schulze JO, Quedenau C, Roske Y, Adam T, Schuler H, Behlke J, Turnbull AP, Sievert V, Scheich C, Mueller U, Heinemann U, Bussow K. Structural and functional characterization of human Iba proteins. FEBS J. 2008 Sep;275(18):4627-40. Epub 2008 Aug 11. PMID:18699778 doi:10.1111/j.1742-4658.2008.06605.x
- ↑ Yamada M, Ohsawa K, Imai Y, Kohsaka S, Kamitori S. X-ray structures of the microglia/macrophage-specific protein Iba1 from human and mouse demonstrate novel molecular conformation change induced by calcium binding. J Mol Biol. 2006 Dec 1;364(3):449-57. Epub 2006 Sep 15. PMID:17011575 doi:10.1016/j.jmb.2006.09.027
