All four members of the Ten-m/Odz family of transmembrane proteins form dimers
All four members of the Ten-m/Odz family of transmembrane proteins form dimers
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DOI：
10.1074/jbc.m203722200
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发表时间：
2002-07-19
影响因子：
4.8
通讯作者：
F채ssler, R
中科院分区：
文献类型：
--
作者：
Feng, K;Zhou, XH;F채ssler, R
Ten-m/Odz/Teneurins是一个新的家族，由四个不同的II型跨膜分子组成。它们的胞外结构域由八个连续的EGF模块组成的阵列，后面跟着一个大的球状结构域。八个模块中有两个只含有5个半胱氨酸残基，而不是典型的6个半胱氨酸残基，并且有能力以共价、二硫键连接的方式进行二聚。利用哺乳动物HEK-293细胞产生的分泌型重组分子分析了所有四种小鼠Ten-m蛋白胞外区的结构特性。超速离心数据支持的电子显微镜分析表明，所有Ten-m蛋白的重组胞外区都形成了同源二聚体。非还原条件下的SDS-PAGE分析以及分子部分变性后的阴性染色表明，Ten-M1和-M4的球状COOH-末端结构域含有对变性剂具有明显稳定性的亚结构域，特别是与Ten-m2和-M3的同源结构域相比。具有两个不同胞外结构域的哺乳动物细胞的共转染实验表明，Ten-m分子也有能力形成异二聚体，这一特性与选择性剪接事件相结合，允许从有限的一组基因中形成多种具有不同特征的分子。
Ten-m/Odz/teneurins are a new family of four distinct type II transmembrane molecules. Their extracellular domains are composed of an array of eight consecutive EGF modules followed by a large globular domain. Two of the eight modules contain only 5 instead of the typical 6 cysteine residues and have the capability to dimerize in a covalent, disulfide-linked fashion. The structural properties of the extracellular domains of all four mouse Ten-m proteins have been analyzed using secreted, recombinant molecules produced by mammalian HEK-293 cells. Electron microscopic analysis supported by analytical ultracentrifugation data revealed that the recombinant extracellular domains of all Ten-m proteins formed homodimers. SDS-PAGE analysis under non-reducing conditions as well as negative staining after partial denaturation of the molecules indicated that the globular COOH-terminal domains of Ten-m1 and -m4 contained subdomains with a pronounced stability against denaturing agents, especially when compared with the homologous domains of Ten-m2 and -m3. Co-transfection experiments of mammalian cells with two different extracellular domains revealed that Ten-m molecules have also the ability to form heterodimers, a property that, combined with alternative splicing events, allows the formation of a multitude of molecules with different characteristics from a limited set of genes.