The assembly of diverse immune receptors is focused on a polar membrane-embedded interaction site.
The assembly of diverse immune receptors is focused on a polar membrane-embedded interaction site.
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DOI：
10.1371/journal.pbio.0040142
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发表时间：
2006-05
期刊：
影响因子：
9.8
通讯作者：
Wucherpfennig KW
中科院分区：
文献类型：
--
作者：
Feng J;Call ME;Wucherpfennig KW
在免疫系统中，大多数负责激活不同细胞类型的受体通过基本跨膜残基与信号二聚体的一对酸性残基的相互作用与二聚体信号模块组装。由于其他膜蛋白的组装需要沿着跨膜螺旋延伸的特定相互作用，我们研究了极性相互作用位点两侧的跨膜序列如何促进与不同信号模块相关的三种受体的组装——自然杀伤细胞受体KIR和NKG2D以及IgA的Fc受体Fcα ri。KIR和NKG2D受体分别与DAP12和DAP10二聚体组装，即使整个KIR或NKG2D跨膜结构域被具有适当定位的基本残基的聚亮氨酸序列所取代。相比之下，由于KIR-DAP12和fc α - ri - fc γ相互作用分别倾向于赖氨酸或精氨酸，因此可以观察到碱性侧链的高度特异性。不相容的膜外结构域之间的空间位阻和信号模块的竞争也有助于组装的特异性。这些结果表明，这些相互作用集中在三个可电离的跨膜残基产生的极性位点上，并解释了DAP12和Fcγ信号传导模块如何与具有高度分散的跨膜序列的大型非重叠受体集合组装。通过突变多种免疫受体中聚亮氨酸的所有残基，作者发现仅需要嵌入膜中的一个极性相互作用就可以实现其特异性和组装。
The majority of receptors responsible for activation of distinct cell types within the immune system assemble with dimeric signaling modules through interaction of a basic transmembrane residue with a pair of acidic residues of the signaling dimer. Because assembly of other membrane proteins requires specific interactions along extended stretches of transmembrane helices, we examined how transmembrane sequences flanking the polar interaction site contribute to assembly for three receptors that associate with different signaling modules—the natural killer cell receptors KIR and NKG2D and the Fc receptor for IgA, FcαRI. The KIR and NKG2D receptors assembled with the DAP12 and DAP10 dimers, respectively, even when the entire KIR or NKG2D transmembrane domains were replaced by polyleucine sequences with a properly positioned basic residue. In contrast, a high degree of specificity for the basic side chain could be observed because the KIR–DAP12 and FcαRI–Fcγ interactions favored lysine or arginine, respectively. Steric hindrance among incompatible extra-membranous domains and competition for signaling modules also contributed to specificity of assembly. These results demonstrate that these interactions are focused on the polar site created by three ionizable transmembrane residues, and explain how the DAP12 and Fcγ signaling modules can assemble with large, non-overlapping sets of receptors that have highly divergent transmembrane sequences. By mutating all residues but one to polyleucine in diverse immune receptors, the authors find that only one polar interaction embedded in the membrane is required for their specificity and assembly.
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影响因子：
5.6
作者：
Dawson, JP;Weinger, JS;Engelman, DM
通讯作者：
Engelman, DM
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
影响因子：
56.9
作者：
MacKenzie, KR;Prestegard, JH;Engelman, DM
通讯作者：
Engelman, DM
影响因子：
4.4
作者：
Dhanji, S;Teh, HS
通讯作者：
Teh, HS
DOI：
10.1084/jem.20042558
发表时间：
2005-04-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Abi-Rached L;Parham P
通讯作者：
Parham P