Structural highlights
Function
S100B_HUMAN Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
S100B is a homodimeric zinc-, copper-, and calcium-binding protein of the family of EF-hand S100 proteins. Zn(2+) binding to S100B increases its affinity towards Ca(2+) as well as towards target peptides and proteins. Cu(2+) and Zn(2+) bind presumably to the same site in S100B. We determined the structures of human Zn(2+)- and Ca(2+)-loaded S100B at pH 6.5, pH 9, and pH 10 by X-ray crystallography at 1.5, 1.4, and 1.65A resolution, respectively. Two Zn(2+) ions are coordinated tetrahedrally at the dimer interface by His and Glu residues from both subunits. The crystal structures revealed that ligand swapping occurs for one of the four ligands in the Zn(2+)-binding sites. Whereas at pH 9, the Zn(2+) ions are coordinated by His15, His25, His 85', and His 90', at pH 6.5 and pH 10, His90' is replaced by Glu89'. The results document that the Zn(2+)-binding sites are flexible to accommodate other metal ions such as Cu(2+). Moreover, we characterized the structural changes upon Zn(2+) binding, which might lead to increased affinity towards Ca(2+) as well as towards target proteins. We observed that in Zn(2+)-Ca(2+)-loaded S100B the C-termini of helix IV adopt a distinct conformation. Zn(2+) binding induces a repositioning of residues Phe87 and Phe88, which are involved in target protein binding.
The crystal structures of human S100B in the zinc- and calcium-loaded state at three pH values reveal zinc ligand swapping.,Ostendorp T, Diez J, Heizmann CW, Fritz G Biochim Biophys Acta. 2010 Oct 13. PMID:20950652[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gilquin B, Cannon BR, Hubstenberger A, Moulouel B, Falk E, Merle N, Assard N, Kieffer S, Rousseau D, Wilder PT, Weber DJ, Baudier J. The calcium-dependent interaction between S100B and the mitochondrial AAA ATPase ATAD3A and the role of this complex in the cytoplasmic processing of ATAD3A. Mol Cell Biol. 2010 Jun;30(11):2724-36. doi: 10.1128/MCB.01468-09. Epub 2010 Mar , 29. PMID:20351179 doi:10.1128/MCB.01468-09
- ↑ Ostendorp T, Diez J, Heizmann CW, Fritz G. The crystal structures of human S100B in the zinc- and calcium-loaded state at three pH values reveal zinc ligand swapping. Biochim Biophys Acta. 2010 Oct 13. PMID:20950652 doi:10.1016/j.bbamcr.2010.10.006
