The crystal structure of human MRP14 (S100A9), a Ca2+-dependent regulator protein in inflammatory process

Human MRP14 (hMRP14) is a Ca2+-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 Ca2+-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 Angstrom 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. (C) 2002 Elsevier Science Ltd.