Structural characterization of a dimerization interface in the CD28 transmembrane domain.
Structural characterization of a dimerization interface in the CD28 transmembrane domain.
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CD28 跨膜域二聚化界面的结构表征。
DOI：
10.1016/j.str.2022.03.004
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发表时间：
2022
期刊：
影响因子：
5.7
通讯作者：
B. Ouyang
中科院分区：
文献类型：
--
作者：
Hongyi Wu;Ruiyu Cao;M. Wen;Hongjuan Xue;B. Ouyang
CD 28通过增强T细胞活化和分化在调节免疫应答中具有关键作用。最近的研究表明，CD 28的跨膜螺旋（TMH）介导受体的组装和活性，但TMH的结构表征仍然缺乏。在这里，我们使用核磁共振（NMR）技术确定了CD 28-TMH的二聚体螺旋-螺旋包装。出乎意料的是，野生型CD 28-TMH单独在脂质双胞中形成稳定的四聚体而不是二聚体。CD 28-TMH C165 F突变体的NMR结构揭示了在许多二聚体组装中高度保守的GxxxA基序位于二聚化界面。突变G160和A164可以破坏跨膜螺旋组装并降低细胞中的CD 28增强。相反，先前提出的YxxxxT基序不影响全长CD 28的二聚化，但它确实影响CD 28活性。这些结果表明，CD 28的跨膜结构域以复杂的方式调节信号转导。
CD28 has a crucial role in regulating immune responses by enhancing T cell activation and differentiation. Recent studies have shown that the transmembrane helix (TMH) of CD28 mediates receptor assembly and activity, but a structural characterization of TMH is still lacking. Here, we determined the dimeric helix-helix packing of CD28-TMH using nuclear magnetic resonance (NMR) technology. Unexpectedly, wild-type CD28-TMH alone forms stable tetramers in lipid bicelles instead of dimers. The NMR structure of the CD28-TMH C165F mutant reveals that a GxxxA motif, which is highly conserved in many dimeric assemblies, is located at the dimerization interface. Mutating G160 and A164 can disrupt the transmembrane helix assembly and reduces CD28 enhancement in cells. In contrast, a previously proposed YxxxxT motif does not affect the dimerization of full-length CD28, but it does affect CD28 activity. These results imply that the transmembrane domain of CD28 regulates the signaling transduction in a complicated manner.
影响因子：
7.2
作者：
Boomer, Jonathan S.;Green, Jonathan M.
通讯作者：
Green, Jonathan M.
影响因子：
32.4
作者：
Zhao, Yunlong;Lee, Calvin K.;Hui, Enfu
通讯作者：
Hui, Enfu
用于蛋白跨膜分区的溶液NMR研究的最佳bicelle尺寸Q。
DOI：
10.1002/chem.201604206
发表时间：
2017-01-26
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Piai A;Fu Q;Dev J;Chou JJ
通讯作者：
Chou JJ