title: The crystal structure of zebrafish S100Z: implications for calcium-promoted S100 protein oligomerisation.
abstract: The S100 family, with about 20 members in humans, is composed of EF-hand calcium-regulated proteins and is linked to a range of serious human diseases, including cancer and autoimmune and neurological disorders. The oldest S100 family members are found in teleosts (bony fish). The zebrafish, Danio rerio, was suggested as a promising model system for in vivo studies on S100 family functions, and we chose to investigate zebrafish S100Z as the closest homologue of the metastasis-promoting human S100A4. Here, we report the first crystal structure of an S100 protein from this organism, the calcium-bound state of S100Z to 2.03 Å resolution. Crystal packing suggests higher-order oligomerisation of S100Z dimers, with a tetramerisation interface very similar to, but even more extensive than, that reported for S100A4. The interactions are primarily through the C-terminal αIV helices from adjacent dimers in an antiparallel orientation. Structural comparisons between known S100 multimeric assemblies together with analysis of calcium-driven changes to the dimerisation cores suggest a mechanism for calcium-promoted oligomerisation of S100 proteins.
authors.affiliation: Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5DD, UK. olga@ysbl.york.ac.uk
authors.forename: Olga V
authors.initials: OV
authors.lastname: Moroz
authors.forename: Igor B
authors.initials: IB
authors.lastname: Bronstein
authors.forename: Keith S
authors.initials: KS
authors.lastname: Wilson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D055503:Protein Multimerization; D009418:S100 Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish
chemical_list: D009418:S100 Proteins; D002118:Calcium