CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence.
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence.
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DOI：
10.1084/jem.20072525
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发表时间：
2008-03-17
期刊：
影响因子：
--
通讯作者：
Rossjohn J
中科院分区：
文献类型：
--
作者：
Petrie EJ;Clements CS;Lin J;Sullivan LC;Johnson D;Huyton T;Heroux A;Hoare HL;Beddoe T;Reid HH;Wilce MC;Brooks AG;Rossjohn J
异源二聚体CD94-NKG2自然杀伤(NK)受体家族识别人类白细胞抗原(HL A)-E是NK细胞监测其他人类白细胞抗原(HL A)-E表达的主要先天机制，但这种高度特异性相互作用的结构基础尚不清楚。在这里，我们描述了CD94-NKG2A的晶体结构，它与人类白细胞抗原-E结合在一个由人类白细胞抗原G的前导序列衍生的多肽上。CD94亚基在与HLAE的相互作用中占主导地位，而NKG2A亚单位则更靠近界面。此外，不变的CD94亚基主导了多肽介导的接触，尽管表面和化学互补性很差。这种不寻常的结合模式与CD94-NKG2A-HLA-E界面的突变数据一致。CD94-NKG2A或HLA-E在结扎后几乎没有构象变化，这种“锁和钥匙”的相互作用是天然受体-配体相互作用的典型特征。然而，该结构也为这种相互作用如何通过肽配体的细微变化或通过CD94与NKG2家族其他成员的配对而调节提供了洞察力。NKG2D和CD94-NKG2A受体使用的对接策略的差异为理解NKG2D与CD94-NKG2受体识别配体的混杂性质提供了基础。
The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A–HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a “lock and key” interaction is typical of innate receptor–ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors.
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MTB衍生的抗原对人CD8+ T细胞的HLA-E依赖性表现。
影响因子：
15.3
作者：
Heinzel, Amy S;Grotzke, Jeff E;Lines, Rebecca A;Lewinsohn, Deborah A;McNabb, Andria L;Streblow, Daniel N;Braud, Veronique M;Grieser, Heather J;Belisle, John T;Lewinsohn, David M
通讯作者：
Lewinsohn, David M
DOI：
10.1084/jem.187.5.813
发表时间：
1998-03-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Borrego F;Ulbrecht M;Weiss EH;Coligan JE;Brooks AG
通讯作者：
Brooks AG
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.4
作者：
Kaiser, BK;Barahmand-pour, F;Strong, RK
通讯作者：
Strong, RK
影响因子：
32.4
作者：
Li, PW;McDermott, G;Strong, RK
通讯作者：
Strong, RK