4xyn | pdb_00004xyn
X-ray structure of Ca(2+)-S100B with human RAGE-derived W61 peptide
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] Publication Abstract from PubMedS100B is a damage-associated molecular pattern protein that, when released into the extracellular milieu, triggers initiation of the inflammatory response through the receptor for advanced glycation end products (RAGE). Recognition of S100B is accomplished via the amino-terminal variable immunoglobulin domain (V-domain) of RAGE. To gain insights into this interaction, a complex between S100B and a 15-amino-acid peptide derived from residues 54-68 of the V-domain was crystallized. The X-ray crystal structure was solved to 2.55 A resolution. There are two dimers of S100B and one peptide in the asymmetric unit. The binding interface of this peptide is compared with that found in the complex between S100B and the 12-amino-acid CapZ-derived peptide TRTK-12. This comparison reveals that although the peptides adopt completely different backbone structures, the residues buried at the interface interact with S100B in similar regions to form stable complexes. The binding affinities of S100B for the intact wild-type V-domain and a W61A V-domain mutant were determined to be 2.7 +/- 0.5 and 1.3 +/- 0.7 microM, respectively, using fluorescence titration experiments. These observations lead to a model whereby conformational flexibility in the RAGE receptor allows the adoption of a binding conformation for interaction with the stable hydrophobic groove on the surface of S100B. Structural insights into the binding of the human receptor for advanced glycation end products (RAGE) by S100B, as revealed by an S100B-RAGE-derived peptide complex.,Jensen JL, Indurthi VS, Neau DB, Vetter SW, Colbert CL Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1176-83. doi:, 10.1107/S1399004715004216. Epub 2015 Apr 25. PMID:25945582[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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