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 (-TΔS=-9.4∼-6.6 kcal mol-1) with low heat capacity changes (ΔCp=-0.22∼-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.
| Original language | English |
|---|---|
| Pages (from-to) | 237-248 |
| Number of pages | 12 |
| Journal | Journal of Molecular Biology |
| Volume | 355 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 13 2006 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Molecular Biology
Cite this
Entropically driven MHC class I recognition by human inhibitory receptor leukocyte Ig-like receptor B1 (LILRB1/ILT2/CD85j). / Shiroishi, Mitsunori; Kuroki, Kimiko; Tsumoto, Kouhei; Yokota, Akiko; Sasaki, Takashi; Amano, Kimie; Shimojima, Tsukasa; Shirakihara, Yasuo; Rasubala, Linda; Van Der Merwe, P. Anton; Kumagai, Izumi; Kohda, Daisuke; Maenaka, Katsumi.
In: Journal of Molecular Biology, Vol. 355, No. 2, 13.01.2006, p. 237-248.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Entropically driven MHC class I recognition by human inhibitory receptor leukocyte Ig-like receptor B1 (LILRB1/ILT2/CD85j)
AU - Shiroishi, Mitsunori
AU - Kuroki, Kimiko
AU - Tsumoto, Kouhei
AU - Yokota, Akiko
AU - Sasaki, Takashi
AU - Amano, Kimie
AU - Shimojima, Tsukasa
AU - Shirakihara, Yasuo
AU - Rasubala, Linda
AU - Van Der Merwe, P. Anton
AU - Kumagai, Izumi
AU - Kohda, Daisuke
AU - Maenaka, Katsumi
PY - 2006/1/13
Y1 - 2006/1/13
N2 - 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∼-6.6 kcal mol-1) with low heat capacity changes (ΔCp=-0.22∼-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.
AB - 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∼-6.6 kcal mol-1) with low heat capacity changes (ΔCp=-0.22∼-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.
UR - http://www.scopus.com/inward/record.url?scp=28844485114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28844485114&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2005.10.057
DO - 10.1016/j.jmb.2005.10.057
M3 - Article
VL - 355
SP - 237
EP - 248
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 2
ER -