Abstract
The functions of the members of the S100 family of EF-hand proteins are modulated by calcium and, in a number of cases, by zinc or copper. One such protein is S100A12, which is implicated in inflammation and host-parasite responses. Previously, we reported the structures of human S100A12 in both low (dimeric) and high (hexameric) calcium forms and, in addition, that of a complex with copper and calcium. Here we report the crystal structures of the metal-free apo form of human S100A12 at 1.77 angstrom resolution and of the zinc complex in two crystal forms (P2(1)2(1)2(1) and F222) to 1.88 angstrom and 1.73 angstrom resolution, respectively. These are the first structures of a zinc-only complex of an S100 protein to be determined. The zinc complex structure shows significant differences from those of both calcium-loaded and apo-S100A12 structures, and comparisons suggest an explanation for the zinc-induced 1500-fold increase in calcium affinity. In addition, the new structures provide insight into the role of zinc-calcium interplay in the transition of S100A12 from a dimer through a tetramer to a hexamer. The role of both zinc and calcium in target binding by S100A12 during host-parasite responses is confirmed by experiments with paramyosin from the tropical parasites Onchocerca volvulus and Brugia malayi. (C) 2009 Elsevier Ltd. All rights reserved.
| Original language | English |
|---|---|
| Pages (from-to) | 536-551 |
| Number of pages | 16 |
| Journal | Journal of Molecular Biology |
| Volume | 391 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 21 Aug 2009 |
Keywords
- S100A12
- X-ray structure
- calcium free
- zinc complex
- paramyosin
- CALCIUM-BINDING PROTEIN
- CALGRANULIN-C
- MOLECULAR-GRAPHICS
- HIGH-AFFINITY
- IDENTIFICATION
- RECEPTOR
- TARGET
- FAMILY
- CA2+
- NOMENCLATURE