Entropically driven MHC class I recognition by human inhibitory receptor leukocyte Ig-like receptor B1 (LILRB1/ILT2/CD85j).
Entropically driven MHC class I recognition by human inhibitory receptor leukocyte Ig-like receptor B1 (LILRB1/ILT2/CD85j).
复制标题
DOI：
10.1016/j.jmb.2005.10.057
复制
发表时间：
2006-01
影响因子：
5.6
通讯作者：
M. Shiroishi;K. Kuroki;K. Tsumoto;A. Yokota;A. Yokota;Takashi Sasaki;K. Amano;T. Shimojima;
中科院分区：
文献类型：
--
作者：
M. Shiroishi;K. Kuroki;K. Tsumoto;A. Yokota;A. Yokota;Takashi Sasaki;K. Amano;T. Shimojima;
人类抑制受体白细胞免疫球蛋白（Ig）样受体B1（也称为Ig样转录物（ILT） 2, CD85j）在白细胞上广泛表达。LILRB1与广泛的主要组织相容性复合体I类分子（MHCIs）结合，并转导负面信号，例如，可以阻止杀死表达mhci的细胞。本文报道了LILRB1识别MHCI的动力学、热力学、核磁共振和晶体学分析。动力学研究表明，LILRB1以快速的结合和解离速率与MHCIs结合，这是典型的细胞-细胞识别受体。热力学分析表明，LILRB1-MHCI相互作用是熵驱动的（−TΔS=−9.4 ~−6.6kcalmol−1），热容量变化较小（ΔCp=−0.22 ~−0.10kcalmol−1K−1）。不同晶型的LILRB1的晶体结构表现出两个n端ig样结构域之间肘关节角的变化，表明了结构域间的灵活性。与此一致的是，核磁共振分析提供了LILRB1在MHCI结合后构象变化的直接证据。这些发现表明，LILRB1-MHCI相互作用虽然涉及一些构象调整，但并不伴随着结合界面构象柔韧性的大幅降低。这种结合模式不同于“诱导契合”结合，后者与构象灵活性的大幅降低有关，并且适合于MHCIs的快速结合，从而能够快速监测MHCIs在靶细胞上的表达水平。
The human inhibitory receptor, leukocyte immunoglobulin (Ig)-like receptor B1 (also called Ig-like transcript (ILT) 2, CD85j), is broadly expressed on leukocytes. LILRB1 binds to a wide range of major histocompatibility complex class I molecules (MHCIs) and transduces negative signals that can, for example, prevent killing of MHCI-expressing cells. Here we report the kinetic, thermodynamic, NMR and crystallographic analyses of MHCI recognition by LILRB1. Kinetic studies demonstrated that LILRB1 binds to MHCIs with fast association and dissociation rates, typical of cell–cell recognition receptors. Thermodynamic analyses showed that LILRB1–MHCI interactions are entropically driven (−TΔS=−9.4∼−6.6kcalmol−1) with low heat capacity changes (ΔCp=−0.22∼−0.10kcalmol−1K−1). The crystal structures of LILRB1 in the different crystal forms exhibited variation in the elbow angle between the two N-terminal Ig-like domains, indicating interdomain flexibility. Consistently, NMR analysis provided the direct evidence of the conformational changes of LILRB1 upon the MHCI binding. These findings suggest that LILRB1–MHCI interactions, while involving some conformational adjustment, are not accompanied by a very large reduction in conformational flexibility at the binding interface. This mode of binding is distinct from “induced-fit” binding, which is associated with large reductions in conformational flexibility, and would be suitable for rapid engagement of MHCIs to enable fast monitoring of the expression level of MHCIs on target cells.