Abstract
S100A12 is a member of the S100 family of EFโhand calciumโbinding proteins. Together with two other calgranulins, S100A8 and S100A9, it is mostly expressed in human granulocytes, although there is increasing evidence of expression in keratinocytes and psoriatic lesions. It is involved in hostโparasite response, and linked to corneal autoimmune diseases connected with filarial parasite infestation. Interaction of S100A12 with a multiligand receptor for advanced glycation end products (RAGE) mediates inflammation. Human recombinant S100A12 was found to induce neuritogenesis of cultured hippocampal cells, similar to two other S100 proteins, S100B and S100A4. Xโray structure of S100A12 has been solved in two crystal forms: R3 and P2~1~. In the R3 crystal form S100A12 is a dimer, and in the P2~1~ crystal form the dimers are arranged as a hexamer. The hexameric form suggests its role in receptor oligomerisation. S100A12 binds copper at the predicted zinc/copper binding site, which is located close to the surface of the protein. We propose copperโmediated generation of reactive oxygen species by S100A12 as its function in hostโparasite response. Microsc. Res. Tech. 60:581โ592, 2003. ยฉ 2003 WileyโLiss, Inc.