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PMID:17011575

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Citation

Yamada, M, Ohsawa, K, Imai, Y, Kohsaka, S and Kamitori, S (2006) 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. 364:449-57

Abstract

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.

Links

PubMed Online version:10.1016/j.jmb.2006.09.027

Keywords

Amino Acid Sequence; Animals; Binding Sites; Calcium/chemistry; Calcium-Binding Proteins/chemistry; Calmodulin/chemistry; Crystallography, X-Ray; DNA-Binding Proteins/chemistry; Humans; Macrophages/metabolism; Mice; Microfilament Proteins; Microglia/metabolism; Models, Molecular; Molecular Sequence Data; Protein Conformation; S100 Proteins/chemistry; Troponin C/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:AIF1

involved_in

GO:0097178: ruffle assembly

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:AIF1

enables

GO:0005509: calcium ion binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:AIF1

involved_in

GO:0001774: microglial cell activation

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:AIF1

involved_in

GO:0097178: ruffle assembly

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:AIF1

enables

GO:0005509: calcium ion binding

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:O70200

F

Seeded From UniProt

complete

HUMAN:AIF1

involved_in

GO:0001774: microglial cell activation

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete


See also

References

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