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2d68

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2d68, resolution 1.60Å ()
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Structure of the N-terminal domain of FOP (FGFR1OP) protein

Publication Abstract from PubMed

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.

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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]

About this Structure

2d68 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Mikolajka A, Yan X, Popowicz GM, Smialowski P, Nigg EA, Holak TA. Structure of the N-terminal domain of the FOP (FGFR1OP) protein and implications for its dimerization and centrosomal localization. J Mol Biol. 2006 Jun 16;359(4):863-75. Epub 2006 Apr 24. PMID:16690081 doi:S0022-2836(06)00474-8
  1. Yan X, Habedanck R, Nigg EA. A complex of two centrosomal proteins, CAP350 and FOP, cooperates with EB1 in microtubule anchoring. Mol Biol Cell. 2006 Feb;17(2):634-44. Epub 2005 Nov 28. PMID:16314388 doi:E05-08-0810

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