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Title: Molecular Architecture of the Major Histocompatibility Complex Class I-Binding Site of Ly49 Natural Killer Cell Receptors

Abstract

Natural killer (NK) cells play a vital role in the detection and destruction of virally infected and tumor cells during innate immune responses. The highly polymorphic Ly49 family of NK receptors regulates NK cell function by sensing major histocompatibility complex class I (MHC-I) molecules on target cells. Despite the determination of two Ly49-MHC-I complex structures, the molecular features of Ly49 receptors that confer specificity for particular MHC-I alleles have not been identified. To understand the functional architecture of Ly49-binding sites, we determined the crystal structures of Ly49C and Ly49G and completed refinement of the Ly49C-H-2Kb complex. This information, combined with mutational analysis of Ly49A, permitted a structure-based classification of Ly49s that we used to dissect the binding site into three distinct regions, each having different roles in MHC recognition. One region, located at the center of the binding site, has a similar structure across the Ly49 family and mediates conserved interactions with MHC-I that contribute most to binding. However, the preference of individual Ly49s for particular MHC-I molecules is governed by two regions that flank the central region and are structurally more variable. One of the flanking regions divides Ly49s into those that recognize both H-2D and H-2K versus onlymore » H-2D ligands, whereas the other discriminates among H-2D or H-2K alleles. The modular design of Ly49-binding sites provides a framework for predicting the MHC-binding specificity of Ly49s that have not been characterized experimentally.« less

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
959586
Report Number(s):
BNL-82572-2009-JA
Journal ID: ISSN 0021-9258; JBCHA3; TRN: US201016%%730
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Journal of Biological Chemistry
Additional Journal Information:
Journal Volume: 283; Journal Issue: 24; Journal ID: ISSN 0021-9258
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; ARCHITECTURE; CLASSIFICATION; CRYSTAL STRUCTURE; DESIGN; DETECTION; FUNCTIONALS; HISTOCOMPATIBILITY COMPLEX; SPECIFICITY; TARGETS; TUMOR CELLS; national synchrotron light source

Citation Formats

Deng, L, Cho, S, Malchiodi, E, Kerzic, M, Dam, J, and Mariuzza, R. Molecular Architecture of the Major Histocompatibility Complex Class I-Binding Site of Ly49 Natural Killer Cell Receptors. United States: N. p., 2008. Web. doi:10.1074/jbc.M801526200.
Deng, L, Cho, S, Malchiodi, E, Kerzic, M, Dam, J, & Mariuzza, R. Molecular Architecture of the Major Histocompatibility Complex Class I-Binding Site of Ly49 Natural Killer Cell Receptors. United States. https://doi.org/10.1074/jbc.M801526200
Deng, L, Cho, S, Malchiodi, E, Kerzic, M, Dam, J, and Mariuzza, R. 2008. "Molecular Architecture of the Major Histocompatibility Complex Class I-Binding Site of Ly49 Natural Killer Cell Receptors". United States. https://doi.org/10.1074/jbc.M801526200.
@article{osti_959586,
title = {Molecular Architecture of the Major Histocompatibility Complex Class I-Binding Site of Ly49 Natural Killer Cell Receptors},
author = {Deng, L and Cho, S and Malchiodi, E and Kerzic, M and Dam, J and Mariuzza, R},
abstractNote = {Natural killer (NK) cells play a vital role in the detection and destruction of virally infected and tumor cells during innate immune responses. The highly polymorphic Ly49 family of NK receptors regulates NK cell function by sensing major histocompatibility complex class I (MHC-I) molecules on target cells. Despite the determination of two Ly49-MHC-I complex structures, the molecular features of Ly49 receptors that confer specificity for particular MHC-I alleles have not been identified. To understand the functional architecture of Ly49-binding sites, we determined the crystal structures of Ly49C and Ly49G and completed refinement of the Ly49C-H-2Kb complex. This information, combined with mutational analysis of Ly49A, permitted a structure-based classification of Ly49s that we used to dissect the binding site into three distinct regions, each having different roles in MHC recognition. One region, located at the center of the binding site, has a similar structure across the Ly49 family and mediates conserved interactions with MHC-I that contribute most to binding. However, the preference of individual Ly49s for particular MHC-I molecules is governed by two regions that flank the central region and are structurally more variable. One of the flanking regions divides Ly49s into those that recognize both H-2D and H-2K versus only H-2D ligands, whereas the other discriminates among H-2D or H-2K alleles. The modular design of Ly49-binding sites provides a framework for predicting the MHC-binding specificity of Ly49s that have not been characterized experimentally.},
doi = {10.1074/jbc.M801526200},
url = {https://www.osti.gov/biblio/959586}, journal = {Journal of Biological Chemistry},
issn = {0021-9258},
number = 24,
volume = 283,
place = {United States},
year = {Tue Jan 01 00:00:00 EST 2008},
month = {Tue Jan 01 00:00:00 EST 2008}
}