title: A structural basis for S100 protein specificity derived from comparative analysis of apo and Ca(2+)-calcyclin.
abstract: Calcyclin is a homodimeric protein belonging to the S100 subfamily of EF-hand Ca(2+)-binding proteins, which function in Ca(2+) signal transduction processes. A refined high-resolution solution structure of Ca(2+)-bound rabbit calcyclin has been determined by heteronuclear solution NMR. In order to understand the Ca(2+)-induced structural changes in S100 proteins, in-depth comparative structural analyses were used to compare the apo and Ca(2+)-bound states of calcyclin, the closely related S100B, and the prototypical Ca(2+)-sensor protein calmodulin. Upon Ca(2+) binding, the position and orientation of helix III in the second EF-hand is altered, whereas the rest of the protein, including the dimer interface, remains virtually unchanged. This Ca(2+)-induced structural change is much less drastic than the "opening" of the globular EF-hand domains that occurs in classical Ca(2+) sensors, such as calmodulin. Using homology models of calcyclin based on S100B, a binding site in calcyclin has been proposed for the N-terminal domain of annexin XI and the C-terminal domain of the neuronal calcyclin-binding protein. The structural basis for the specificity of S100 proteins is discussed in terms of the variation in sequence of critical contact residues in the common S100 target-binding site.
authors.affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratory, Stockholm University, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Mäler
authors.forename: Mallika
authors.initials: M
authors.lastname: Sastry
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Chazin
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D008958:Models, Molecular; D009414:Nerve Growth Factors / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011817:Rabbits; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D002147:Calmodulin; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D016159:Tumor Suppressor Protein p53; D002118:Calcium