The Crystal Structure of Zebrafish S100Z: Implications for Calcium-Promoted S100 Protein Oligomerisation

Olga V. Moroz, Igor B. Bronstein, Keith S. Wilson

Research output: Contribution to journalArticlepeer-review

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 angstrom 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 alpha IV 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. (C) 2011 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1072-1082
Number of pages11
JournalJournal of Molecular Biology
Volume411
Issue number5
DOIs
Publication statusPublished - 2 Sept 2011

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