X-ray structures of the microglia/macrophage-specific protein Iba1 from human and mouse demonstrate novel molecular conformation change induced by calcium binding.
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.
Yamada
Mitsugu
M
Information Technology Center and Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Ohsawa
Keiko
K
Imai
Yoshinori
Y
Kohsaka
Shinichi
S
Kamitori
Shigehiro
S
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry*; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D009418:S100 Proteins / Q000737:chemistry; D019209:Troponin C / Q000737:chemistry
C112986:AIF1 protein, human; C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D009418:S100 Proteins; D019209:Troponin C; D002118:Calcium