title: Biophysical and Structural Characterization of the Centriolar Protein Cep104 Interaction Network.
abstract: Dysfunction of cilia is associated with common genetic disorders termed ciliopathies. Knowledge on the interaction networks of ciliary proteins is therefore key for understanding the processes that are underlying these severe diseases and the mechanisms of ciliogenesis in general. Cep104 has recently been identified as a key player in the regulation of cilia formation. Using a combination of sequence analysis, biophysics, and x-ray crystallography, we obtained new insights into the domain architecture and interaction network of the Cep104 protein. We solved the crystal structure of the tumor overexpressed gene (TOG) domain, identified Cep104 as a novel tubulin-binding protein, and biophysically characterized the interaction of Cep104 with CP110, Cep97, end-binding (EB) protein, and tubulin. Our results represent a solid platform for the further investigation of the microtubule-EB-Cep104-tubulin-CP110-Cep97 network of proteins. Ultimately, such studies should be of importance for understanding the process of cilia formation and the mechanisms underlying different ciliopathies.
authors.affiliation: From the Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland and.
authors.forename: Lenka
authors.initials: L
authors.lastname: Rezabkova
authors.affiliation: From the Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland and.
authors.forename: Sebastian H W
authors.initials: SH
authors.lastname: Kraatz
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.affiliation: From the Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland and.
authors.forename: Michel O
authors.initials: MO
authors.lastname: Steinmetz
authors.affiliation: From the Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland and richard.kammerer@psi.ch.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kammerer
mesh_terms: D002502:Centrioles / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002923:Cilia / Q000737:chemistry / Q000378:metabolism; D000072661:Ciliopathies / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains
chemical_list: C454180:CKAP5 protein, human; D008869:Microtubule-Associated Proteins
keywords: Cep104; TOG domain; biophysics; centriole; cilia; circular dichroism (CD); x-ray crystallography