%0 Journal Article
%T Structural characterization of S100A15 reveals a novel zinc coordination site among S100 proteins and altered surface chemistry with functional implications for receptor binding
%A Jill I Murray
%A Michelle L Tonkin
%A Amanda L Whiting
%A Fangni Peng
%A Benjamin Farnell
%A Jay T Cullen
%A Fraser Hof
%A Martin J Boulanger
%J BMC Structural Biology
%D 2012
%I BioMed Central
%R 10.1186/1472-6807-12-16
%X To investigate the structural and functional consequences of these divergent clusters, we report the X-ray crystal structures of S100A15 and S100A7D24G, a hybrid variant where the zinc ligand Asp24 of S100A7 has been substituted with the glycine of S100A15, to 1.7£¿£¿ and 1.6£¿£¿ resolution, respectively. Remarkably, despite replacement of the Asp ligand, zinc binding is retained at the S100A15 dimer interface with distorted tetrahedral geometry and a chloride ion serving as an exogenous fourth ligand. Zinc binding was confirmed using anomalous difference maps and solution binding studies that revealed similar affinities of zinc for S100A15 and S100A7. Additionally, the predicted receptor-binding surface on S100A7 is substantially more basic in S100A15 without incurring structural rearrangement.Here we demonstrate that S100A15 retains the ability to coordinate zinc through incorporation of an exogenous ligand resulting in a unique zinc-binding site among S100 proteins. The altered surface chemistry between S100A7 and S100A15 that localizes to the predicted receptor binding site is likely responsible for the differential recognition of distinct protein targets. Collectively, these data provide novel insight into the structural and functional consequences of the divergent surfaces between S100A7 and S100A15 that may be exploited for targeted therapies.The S100 calcium-binding protein family of vertebrate, metal-regulated proteins plays pivotal roles in a wide variety of intracellular and extracellular functions including cell growth, inflammation, membrane remodeling and chemotaxis [1,2] and are implicated in many diseases including cancer [3-6]. Hallmarks of the S100 protein family include their small size (~ 100 aa) and the presence of a canonical (calmodulin-like) EF-hand motif and a non-canonical (S100-specific) EF-hand motif [7]. Additional complexity in S100 proteins is derived from their ability to adopt a non-covalent anti-parallel homo/heterodimers that can furth
%K S100A15
%K S100A7
%K Zinc-binding
%K EF hand
%K X-ray crystallography
%U http://www.biomedcentral.com/1472-6807/12/16