The crystal structure of human MRP14 (S100A9), a Ca(2+)-dependent regulator protein in inflammatory process.
Human MRP14 (hMRP14) is a Ca(2+)-binding protein from the S100 family of proteins. This protein is co-expressed with human MRP8 (hMRP8), a homologue protein in myeloid cells, and plays an indispensable role in Ca(2+)-dependent functions during inflammation. This role includes the activation of Mac-1, the beta(2) integrin which is involved in neutrophil adhesion to endothelial cells. The crystal structure of the holo form of hMRP14 was analyzed at 2.1 A resolution. hMRP14 is distinguished from other S100 member proteins by its long C-terminal region, and its structure shows that the region is extensively flexible. In this crystal structure of hMRP14, Chaps molecules bind to the hinge region that connects two EF-hand motifs, which suggests that this region is a target-binding site of this protein. Based on a structural comparison of hMRP14 with hMRP8 and human S100A12 (hS100A12) that is another homologue protein, the character of MRP8/14 hetero-complex and the functional significance of the flexibility of the C-terminal region of hMRP14 are discussed.
Itou
Hiroshi
H
Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
Yao
Min
M
Fujita
Ikuko
I
Watanabe
Nobuhisa
N
Suzuki
Masaki
M
Nishihira
Jun
J
Tanaka
Isao
I
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D040502:Calgranulin B; D018360:Crystallography, X-Ray; D019281:Dimerization; D020832:EF Hand Motifs; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007249:Inflammation; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D018583:Pliability; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D009418:S100 Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D055672:Static Electricity
D000943:Antigens, Differentiation; D040502:Calgranulin B; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D009418:S100 Proteins; D002118:Calcium