Structure of the N-terminal domain of the FOP (FGFR1OP) protein and implications for its dimerization and centrosomal localization
Structure of the N-terminal domain of the FOP (FGFR1OP) protein and implications for its dimerization and centrosomal localization
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DOI：
10.1016/j.jmb.2006.03.070
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发表时间：
2006-06-16
影响因子：
5.6
通讯作者：
Holak, Tad A.
中科院分区：
文献类型：
--
作者：
Mikolajka, Aleksandra;Yan, Xiumin;Holak, Tad A.
成纤维细胞生长因子受体1 （FGFR1）癌基因伴侣FOP是一种中心体蛋白，参与微管（NITS）锚定到亚细胞结构。该蛋白最初是作为FGFR1在引起干细胞骨髓增殖性疾病的癌蛋白中的融合伙伴被发现的。随后的蛋白质组学筛选鉴定出FOP是中心体的一个组成部分。FOP含有一个Lis-homology （LisH）基序，在100多种真核蛋白中发现。LisH基序被认为与微管动力学和组织、细胞迁移和染色体分离有关；其中一些与遗传疾病有关。本文报道了FOP的n端二聚化畴的1.6埃分辨率晶体结构。该结构包括由两条反平行链组成的α螺旋束，每条链有五个α螺旋。二聚体的中心部分包含LisH结构域。我们进一步确定，FOP的LisH结构域是一个较长的n端片段的一部分，这对于FOP的二聚化和中心体定位是必需的，尽管不是充分的。(c) 2006 Elsevier Ltd.版权所有。
The fibroblast growth factor receptor 1 (FGFR1) oncogene partner, FOP, is a centrosomal protein that is involved in the anchoring of microtubules (NITS) 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 1.6 angstrom 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. (c) 2006 Elsevier Ltd. All rights reserved.