| Structural highlights
Function
[AIF1_MOUSE] 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] [4] [5]
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[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Watano K, Iwabuchi K, Fujii S, Ishimori N, Mitsuhashi S, Ato M, Kitabatake A, Onoe K. Allograft inflammatory factor-1 augments production of interleukin-6, -10 and -12 by a mouse macrophage line. Immunology. 2001 Nov;104(3):307-16. PMID:11722645
- ↑ Ohsawa K, Imai Y, Kanazawa H, Sasaki Y, Kohsaka S. Involvement of Iba1 in membrane ruffling and phagocytosis of macrophages/microglia. J Cell Sci. 2000 Sep;113 ( Pt 17):3073-84. PMID:10934045
- ↑ Sasaki Y, Ohsawa K, Kanazawa H, Kohsaka S, Imai Y. Iba1 is an actin-cross-linking protein in macrophages/microglia. Biochem Biophys Res Commun. 2001 Aug 17;286(2):292-7. PMID:11500035 doi:http://dx.doi.org/10.1006/bbrc.2001.5388
- ↑ Kanazawa H, Ohsawa K, Sasaki Y, Kohsaka S, Imai Y. Macrophage/microglia-specific protein Iba1 enhances membrane ruffling and Rac activation via phospholipase C-gamma -dependent pathway. J Biol Chem. 2002 May 31;277(22):20026-32. Epub 2002 Mar 26. PMID:11916959 doi:http://dx.doi.org/10.1074/jbc.M109218200
- ↑ Ohsawa K, Imai Y, Sasaki Y, Kohsaka S. Microglia/macrophage-specific protein Iba1 binds to fimbrin and enhances its actin-bundling activity. J Neurochem. 2004 Feb;88(4):844-56. PMID:14756805
- ↑ 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
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