title: Structure of the N-terminal domain of the FOP (FGFR1OP) protein and implications for its dimerization and centrosomal localization.
abstract: The fibroblast growth factor receptor 1 (FGFR1) oncogene partner, FOP, is a centrosomal protein that is involved in the anchoring of microtubules (MTS) to subcellular structures. The protein was originally discovered as a fusion partner with FGFR1 in oncoproteins that give rise to stem cell myeloproliferative disorders. A subsequent proteomics screen identified FOP as a component of the centrosome. FOP contains a Lis-homology (LisH) motif found in more than 100 eukaryotic proteins. LisH motifs are believed to be involved in microtubule dynamics and organization, cell migration, and chromosome segregation; several of them are associated with genetic diseases. We report here a 1.6A resolution crystal structure of the N-terminal dimerization domain of FOP. The structure comprises an alpha-helical bundle composed of two antiparallel chains, each of them having five alpha-helices. The central part of the dimer contains the LisH domain. We further determined that the FOP LisH domain is part of a longer N-terminal segment that is required, albeit not sufficient, for dimerization and centrosomal localization of FOP.
authors.affiliation: Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Mikolajka
authors.forename: Xiumin
authors.initials: X
authors.lastname: Yan
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Popowicz
authors.forename: Pawel
authors.initials: P
authors.lastname: Smialowski
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.forename: Tad A
authors.initials: TA
authors.lastname: Holak
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018385:Centrosome / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D040681:Structural Homology, Protein
chemical_list: C117597:CEP43 protein, human; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins