title: A novel calcium-sensitive switch revealed by the structure of human S100B in the calcium-bound form.
abstract: BACKGROUND
  S100B is a homodimeric member of the EF-hand calcium-binding protein superfamily. The protein has been implicated in cellular processes such as cell differentiation and growth, plays a role in cytoskeletal structure and function, and may have a role in neuropathological diseases, such as Alzheimers. The effects of S100B are mediated via its interaction with target proteins. While several studies have suggested that this interaction is propagated through a calcium-induced conformational change, leading to the exposure of a hydrophobic region of S100B, the molecular details behind this structural alteration remain unclear.
  
  
  RESULTS
  The solution structure of calcium-saturated human S100B (Ca(2+)-S100B) has been determined by heteronuclear NMR spectroscopy. Ca(2+)-S100B forms a well defined globular structure comprising four EF-hand calcium-binding sites and an extensive hydrophobic dimer interface. A comparison of Ca(2+)-S100B with apo S100B and Ca(2+)-calbindin D9k indicates that while calcium-binding to S100B results in little change in the site I EF-hand, it induces a backbone reorientation of the N terminus of the site II EF-hand. This reorientation leads to a dramatic change in the position of helix III relative to the other helices.
  
  
  CONCLUSIONS
  The calcium-induced reorientation of calcium-binding site II results in the increased exposure of several hydrophobic residues in helix IV and the linker region. While following the general mechanism of calcium modulatory proteins, whereby a hydrophobic target site is exposed, the 'calcium switch' observed in S100B appears to be unique from that of other EF-hand proteins and may provide insights into target specificity among calcium modulatory proteins.
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, Canada.
authors.forename: S P
authors.initials: SP
authors.lastname: Smith
authors.forename: G S
authors.initials: GS
authors.lastname: Shaw
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001059:Apoproteins / Q000737:chemistry; D064026:Calbindins; D002118:Calcium / Q000737:chemistry*; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D002417:Cattle; D018797:Cell Cycle Proteins; D019281:Dimerization; D006801:Humans; D009414:Nerve Growth Factors / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D000075383:S100 Calcium Binding Protein A6; D064030:S100 Calcium Binding Protein G / Q000737:chemistry; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D013499:Surface Properties
chemical_list: D000596:Amino Acids; D001059:Apoproteins; D064026:Calbindins; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D009414:Nerve Growth Factors; D000075383:S100 Calcium Binding Protein A6; D064030:S100 Calcium Binding Protein G; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C576506:S100G protein, human; C489132:S100a6 protein, rat; C579158:S100b protein, rat; C576508:S100g protein, rat; C055351:S100A6 protein, human; D002118:Calcium