1mho | pdb_00001mho
THE 2.0 A STRUCTURE OF HOLO S100B FROM BOVINE BRAIN
Structural highlights
Function[S100B_BOVIN] 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. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).[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 PubMedBACKGROUND: S100B, a small acidic calcium-binding protein, is a member of the S100 protein family and is a multifunctional protein capable of binding several target molecules, such as cytoskeletal proteins and protein kinases, in a calcium-dependent manner. S100B is a homodimer of S100 beta subunits (beta beta) with a total of four calcium-binding motifs called EF hands. S100B is found abundantly in nervous tissue and has been implicated in Alzheimer's disease and Down's syndrome. Structural analysis of S100B in the calcium-bound state is required to gain a better understanding of the conformational changes that occur to S100B upon calcium binding and to elucidate the mode of recognition between S100B and its target molecules. RESULTS: We have determined the three-dimensional structure of holo S100B from bovine brain at 2.0 A resolution by X-ray diffraction. The dimeric S100B molecule is formed by non-covalent interactions between large hydrophobic surfaces on both S100 beta subunits. There are two EF-hand motifs per S100 beta subunit, each of which binds one calcium ion. We observe, in the calcium-bound structure, dramatic changes in the conformation of the terminal helices, from the compact structure in the apo form to a more extended form upon binding calcium. Following these changes, an exposed hydrophobic core, surrounded by many negatively charged residues, is revealed. Cys84 is positioned at an exposed surface of S100B, surrounded by hydrophobic residues, and could form a disulfide bond to tau protein, one of the known target molecules thought to interact with S100B in this way. CONCLUSIONS: The molecular structure of holo S100B suggests a novel mode of target recognition for the S100 family of calcium-binding proteins. Upon calcium binding, dramatic changes occur in the terminal helices of S100B, revealing a large hydrophobic surface, not observed in the apo form. It is through hydrophobic interactions and possibly a Cys84-mediated disulfide bond that S100B is thought to bind its target molecules. A novel mode of target recognition suggested by the 2.0 A structure of holo S100B from bovine brain.,Matsumura H, Shiba T, Inoue T, Harada S, Kai Y Structure. 1998 Feb 15;6(2):233-41. PMID:9519413[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
