2d68
From Proteopedia
Structure of the N-terminal domain of FOP (FGFR1OP) protein
Structural highlights
Disease[FR1OP_HUMAN] Note=A chromosomal aberration involving FGFR1OP may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity. Function[FR1OP_HUMAN] Required for anchoring microtubules to the centrosomes.[1] Publication Abstract from PubMedThe 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. Structure of the N-terminal domain of the FOP (FGFR1OP) protein and implications for its dimerization and centrosomal localization.,Mikolajka A, Yan X, Popowicz GM, Smialowski P, Nigg EA, Holak TA J Mol Biol. 2006 Jun 16;359(4):863-75. Epub 2006 Apr 24. PMID:16690081[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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