title: Entropically driven MHC class I recognition by human inhibitory receptor leukocyte Ig-like receptor B1 (LILRB1/ILT2/CD85j).
abstract: 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 (-TdeltaS = -9.4 approximately -6.6 kcal mol(-1)) with low heat capacity changes (deltaC(p) = -0.22 approximately -0.10 kcal mol(-1) K(-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.
authors.affiliation: Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Shiroishi
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kuroki
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Yokota
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kimie
authors.initials: K
authors.lastname: Amano
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Shimojima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shirakihara
authors.forename: Linda
authors.initials: L
authors.lastname: Rasubala
authors.forename: P Anton
authors.initials: PA
authors.lastname: van der Merwe
authors.forename: Izumi
authors.initials: I
authors.lastname: Kumagai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kohda
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
mesh_terms: D015703:Antigens, CD / Q000737:chemistry*; D003461:Crystallography; D019277:Entropy; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry*; D020349:Surface Plasmon Resonance
chemical_list: D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic