First-row transition metal ions are essential nutrients for all organisms.  Metal-ion withholding is one accepted mechanism of innate immunity used by the vertebrate host to prevent microbial replication. In this strategy, the host employs an arsenal of metal-chelating proteins to limit the bioavailability of nutrient metals such as Mn(II), Fe(II) and Zn(II) at sites of infection. Human calprotectin is an abundant metal-sequestering protein that is produced and released by neutrophils. It inhibits the growth of a broad spectrum of bacteria and fungi by depriving these organisms of nutrient metals. Calprotectin exhibits remarkable biological coordination chemistry. It houses six metal-binding sites per S100A8/S100A9 heterodimer. Each S100 submit contains two EF-hand domains for Ca(II) ions, and two sites for transition metals form at the S100A8/S100A9 interface. On the basis of biochemical and biophysical studies, we present a working model whereby calprotectin uses Ca(II) ions to enhance its capacity to sequester transition metals and thereby compete with invading microbes for these important nutrients.  <br/>

Metals and Immunity

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.