Crystal structure of the Ly49I natural killer cell receptor reveals variability in dimerization mode within the Ly49 family

被引:25
作者
Dimasi, N
Sawicki, MW
Reineck, LA
Li, YL
Natarajan, K
Margulies, DH
Mariuzza, RA
机构
[1] Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD 20850 USA
[2] NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA
关键词
natural killer cells; NK cell receptors; MHC class I; X-ray crystallography;
D O I
10.1016/S0022-2836(02)00498-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Natural killer (NK) cells play a crucial role in the detection and destruction of virally infected and tumor cells during innate immune responses. The cytolytic activity of NK cells is regulated through a balance of inhibitory and stimulatory signals delivered by NK receptors that recognize classical major histocompatabilty complex class I (MHC-I) molecules, or MHC-I homologs such as MICA, on target cells. The Ly49 family of NK receptors (Ly49A through W), which includes both inhibitory and activating receptors, are homodimeric type II transmembrane glycoproteins, with each subunit composed of a C-type lectin-like domain tethered to the membrane by a stalk region. We have determined the crystal structure, at 3.0 Angstrom resolution, of the murine inhibitory NK receptor Ly491. The Ly491 monomer adopts a fold similar to that of other C-type lectin-like NK receptors, including Ly49A, NKG2D and CD69. However, the Ly491 monomers associate in a manner distinct from that of these other NK receptors, forming a more open dimer. As a result, the putative MHC-binding surfaces of the Ly491 dimer are spatially more distant than the corresponding surfaces of Ly49A or NKG2D. These structural differences probably reflect the fundamentally different ways in which Ly49 and NKG2D receptors recognize their respective ligands: whereas the single MICA binding site of NKG2D is formed by the precise juxtaposition of two monomers, each Ly49 monomer contains an independent binding site for MHC-I. Hence, the structural constraints on dimerization geometry may be relatively relaxed within the Ly49 family. Such variability may enable certain Ly49 receptors, like Ly491, to bind MHC-I molecules bivalently, thereby stabilizing receptor-ligand interactions and enhancing signal transmission to the NK cell. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:573 / 585
页数:13
相关论文
共 42 条
  • [1] The ever-expanding Ly49 gene family:: repertoire and signaling
    Anderson, SK
    Ortaldo, JR
    McVicar, DW
    [J]. IMMUNOLOGICAL REVIEWS, 2001, 181 : 79 - 89
  • [2] Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors
    Arase, H
    Mocarski, ES
    Campbell, AE
    Hill, AB
    Lanier, LL
    [J]. SCIENCE, 2002, 296 (5571) : 1323 - 1326
  • [3] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY
    BAILEY, S
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 : 760 - 763
  • [4] Natural killer cells in antiviral defense: Function and regulation by innate cytokines
    Biron, CA
    Nguyen, KB
    Pien, GC
    Cousens, LP
    Salazar-Mather, TP
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 : 189 - 220
  • [5] Structure of CD94 reveals a novel C-type lectin fold: Implications for the NK cell-associated CD94/NKG2 receptors
    Boyington, JC
    Riaz, AN
    Patamawenu, A
    Coligan, JE
    Brooks, AG
    Sun, PD
    [J]. IMMUNITY, 1999, 10 (01) : 75 - 82
  • [6] Structure of killer cell immunoglobulin-like receptors and their recognition of the class I MHC molecules
    Boyington, JC
    Brooks, AG
    Sun, PD
    [J]. IMMUNOLOGICAL REVIEWS, 2001, 181 : 66 - 78
  • [7] Recognition of class I major histocompatibility complex molecules by Ly-49: Specificities and domain interactions
    Brennan, J
    Mahon, G
    Mager, DL
    Jefferies, WA
    Takei, F
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (04) : 1553 - 1559
  • [8] Crystallography & NMR system:: A new software suite for macromolecular structure determination
    Brunger, AT
    Adams, PD
    Clore, GM
    DeLano, WL
    Gros, P
    Grosse-Kunstleve, RW
    Jiang, JS
    Kuszewski, J
    Nilges, M
    Pannu, NS
    Read, RJ
    Rice, LM
    Simonson, T
    Warren, GL
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 : 905 - 921
  • [9] A NATURAL-KILLER-CELL RECEPTOR-SPECIFIC FOR A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE
    DANIELS, BF
    KARLHOFER, FM
    SEAMAN, WE
    YOKOYAMA, WM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (02) : 687 - 692
  • [10] C-type lectin-like domains
    Drickamer, K
    [J]. CURRENT OPINION IN STRUCTURAL BIOLOGY, 1999, 9 (05) : 585 - 590