title: Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P.
abstract: S100 proteins are EF hand type Ca2+ binding proteins thought to function in stimulus-response coupling by binding to and thereby regulating cellular targets in a Ca2+-dependent manner. To isolate such target(s) of the S100P protein we devised an affinity chromatography approach that selects for S100 protein ligands requiring the biologically active S100 dimer for interaction. Hereby we identify ezrin, a membrane/F-actin cross-linking protein, as a dimer-specific S100P ligand. S100P-ezrin complex formation is Ca2+ dependent and most likely occurs within cells because both proteins colocalize at the plasma membrane after growth factor or Ca2+ ionophore stimulation. The S100P binding site is located in the N-terminal domain of ezrin and is accessible for interaction in dormant ezrin, in which binding sites for F-actin and transmembrane proteins are masked through an association between the N- and C-terminal domains. Interestingly, S100P binding unmasks the F-actin binding site, thereby at least partially activating the ezrin molecule. This identifies S100P as a novel activator of ezrin and indicates that activation of ezrin's cross-linking function can occur directly in response to Ca2+ transients.
authors.affiliation: Institute for Medical Biochemistry, University of Muenster, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Koltzscher
authors.forename: Claudia
authors.initials: C
authors.lastname: Neumann
authors.forename: Simone
authors.initials: S
authors.lastname: König
authors.forename: Volker
authors.initials: V
authors.lastname: Gerke
mesh_terms: D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002846:Chromatography, Affinity; D003598:Cytoskeletal Proteins; D019281:Dimerization; D017930:Genes, Reporter; D006801:Humans; D009363:Neoplasm Proteins; D010750:Phosphoproteins / Q000378:metabolism*; D000099149:Ezrin
chemical_list: D000199:Actins; D002118:Calcium; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D000099149:Ezrin; C103003:S100P protein, human