Amino Acids

, Volume 41, Issue 4, pp 761–772 | Cite as

The role of zinc in the S100 proteins: insights from the X-ray structures

  • Olga V. MorozEmail author
  • Keith S. Wilson
  • Igor B. BronsteinEmail author
Review Article


We here aim to summarise the present knowledge on zinc binding by S100 proteins. While the importance of modulation of the function of the S100 family of EF-hand proteins by calcium is well established, a substantial proportion is also regulated by zinc or copper. Indeed regulation by zinc in addition to calcium was suggested almost as soon as the first S100 protein was discovered and has been confirmed for many family members by numerous experiments. For the first, “His-Zn”, group, zinc-binding sites composed of three histidines and an aspartic acid were first proposed based on sequence comparisons and later confirmed by structural studies. A second, “Cys-Zn”, group lacks such well-defined zinc-binding motifs and for these cysteines were suggested as the main zinc ligands. There is no three-dimensional structure for a Cys-Zn S100 in the presence of zinc. However, analysis of their sequences together with their X-ray structures in the absence of zinc suggests the possibility of two zinc-binding sites: a conserved site with a degree of similarity to those of the His-Zn group and a less-defined site with a Cys interdimer-binding motif. Some S100 protein-mediated events, such as signalling in the extracellular space, where the levels of calcium are already high, are most unlikely to be calcium regulated. Therefore, a broader knowledge of the role of zinc in the functioning of the S100 proteins will add significantly to the understanding how they propagate their signals.


S100 proteins Zinc Zinc-binding site X-ray structure Extracellular signalling 



Protein data bank





This work was supported by European Commission funding through the SPINE2–COMPLEXES project LSHG–CT–2006–031220. We thank Alexei Murzin for the useful discussions of oligomerisation interfaces.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Structural Biology Laboratory, Department of ChemistryUniversity of YorkYorkUK
  2. 2.School of Biomedical and Health Sciences, Hodgkin Building, Guy’s CampusKing’s CollegeLondonUK

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