The structure of the ζζ transmembrane dimer reveals features essential for its assembly with the T cell receptor
The structure of the ζζ transmembrane dimer reveals features essential for its assembly with the T cell receptor
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DOI：
10.1016/j.cell.2006.08.044
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发表时间：
2006-10-20
期刊：
影响因子：
64.5
通讯作者：
Wucherpfennig, Kai W.
中科院分区：
文献类型：
--
作者：
Call, Matthew E.;Schnell, Jason R.;Wucherpfennig, Kai W.
T细胞受体（TCR）α β异二聚体通过非共价缔合的CD 3 γ-κ、CD 3 δ-κ和xixi二聚体将配体结合传递至细胞内部。虽然TCR-CD 3复合物的细胞外组分的结构是已知的，但介导组装的跨膜（TM）结构域尚未进行结构表征。已知引入xi xi信号传导模块需要一个碱性TCR α和两个xi xi天冬氨酸TM残基。我们报告的核磁共振结构的xi xi（TM）晚餐，一个左手线圈线圈与大量的极性接触。诱变实验表明，三个极性位置对于xi xi二聚化和与TCR组装是关键的。两个天冬氨酸在通过大量氢键稳定的界面处产生单个结构单元，并且有证据表明结构水分子（或分子）紧密接近。这个结构单元，仅代表迄今为止解决的第二个跨膜晚餐界面，作为TCR信号传导中涉及的所有模块的组装的范例。
The T cell receptor (TCR) alpha beta heterodimer communicates ligand binding to the cell interior via noncovalently associated CD3 gamma epsilon, CD3 delta epsilon, and xi xi dimers. While structures of extracellular components of the TCR-CD3 complex are known, the transmembrane (TM) domains that mediate assembly have eluded structural characterization. Incorporation of the xi xi signaling module is known to require one basic TCR alpha and two xi xi aspartic acid TM residues. We report the NMR structure of the xi xi(TM) dinner, a left-handed coiled coil with substantial polar contacts. Mutagenesis experiments demonstrate that three polar positions are critical for xi xi dimerization and assembly with TCR. The two aspartic acids create a single structural unit at the a interface stabilized by extensive hydrogen bonding, and there is evidence for a structural water molecule (or molecules) within close proximity. This structural unit, representing only the second transmembrane dinner interface solved to date, serves as a paradigm for the assembly of all modules involved in TCR signaling.