Molecular competition for NKG2D: H60 and RAE1 compete unequally for NKG2D with dominance of H60
Molecular competition for NKG2D: H60 and RAE1 compete unequally for NKG2D with dominance of H60
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DOI：
10.1016/s1074-7613(01)00187-x
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发表时间：
2001-08-01
期刊：
影响因子：
32.4
通讯作者：
Bjorkman, PJ
中科院分区：
文献类型：
--
作者：
O'Callaghan, CA;Cerwenka, A;Bjorkman, PJ
NKG 2D是自然杀伤细胞、T细胞和巨噬细胞上的强效活化受体。小鼠NKG 2D与两种与I类MHC分子相关的细胞表面配体相互作用：RAE 1和H60。我们使用可溶性形式的NKG 2D、RAE 1和H60来表征它们的相互作用。RAE 1和H60各自以纳摩尔亲和力结合NKG 2D，表明比大多数细胞表面免疫相互作用更紧密的结合，但NKG 2D以比RAE 1高25倍的亲和力结合H60。RAE 1和H60直接竞争NKG 2D的占据，因此NKG 2D一次只能被一个配体占据。与NKG 2D-RAE 1相互作用相比，NKG 2D-H60相互作用更依赖于温度，并且更多地利用静电相互作用。不同的热力学配置文件提供了深入了解不同的分子机制的结合相互作用。
NKG2D is a potent activating receptor on natural killer cells, T cells, and macrophages. Mouse NKG2D interacts with two cell surface ligands related to class I MHC molecules: RAE1 and H60. We used soluble versions of NKG2D, RAE1, and H60 to characterize their interactions. RAE1 and H60 each bind NKG2D with nanomolar affinities, indicating tighter binding than most cell surface immune interactions, but NKG2D binds to H60 with similar to 25-fold higher affinity than to RAE1. RAE1 and H60 compete directly for occupancy of NKG2D, and, thus, NKG2D can be occupied by only one ligand at a time. The NKG2D-H60 interaction is more temperature dependent and makes greater use of electrostatic interactions than the NKG2D-RAE1 interaction. The distinct thermodynamic profiles provide insights into the different molecular mechanisms of the binding interactions.