Structural basis of the differential stability and receptor specificity of H-2Db in complex with murine versus human β2-microglobulin

被引:28
作者
Achour, A [1 ]
Michaëlsson, T
Harris, RA
Ljunggren, HG
Kärre, M
Schneider, G
Sandalova, T
机构
[1] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Med,Ctr Infect Med F59, Stockholm, Sweden
[2] Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden
[3] Karolinska Univ Hosp Solna, Ctr Mol Med, Karolinska Inst, Stockholm, Sweden
[4] Karolinska Inst, IRIS, Strateg Res Ctr, Stockholm, Sweden
[5] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden
关键词
crystal structure; beta(2)-microglobulin; MHC; Ly49; peptide;
D O I
10.1016/j.jmb.2005.11.068
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
beta(2)-Microglobulin (beta(2)m) is non-covalently linked to the major histocompatibility complex (MHC) class I heavy chain and interacts with CD8 and Ly49 receptors. Murine MHC class I heavy chains can bind human beta(2)m (h beta(2)m) and peptide, and such hybrid molecules are often used in structural and functional studies. The replacement of mouse beta(2)m (m beta(2)m) with h beta(2)m has several functional consequences for MHC class I complex stability and specificity, but the structural basis for this is presently unknown. To investigate the impact of species-specific beta(2)m subunits on MHC class I conformation, we provide a crystallographic comparison of H-2D(b) in complex with LCMV-derived gp33 peptide and either h beta(2)m or m beta(2)m. The conformation of the gp33 peptide is not affected by the beta(2)m species. Comparison of the interface between beta(2)m and the alpha(1)alpha(2) domains of the heavy chain in these two crystal structures reveals a marked increase in both polarity and number of hydrogen bonds between h beta(2)m and the alpha(1)alpha(2) domains of H-2D(b). We propose that the positioning of two hydrogen bond rich regions at the h beta(2)m/alpha(1)alpha(2) interface plays a central role in the increased overall stability and peptide exchange capacity in the H-2D(b)/h beta(2)m complex. These two regions act as bridges, holding and stabilizing the underside of the alpha(1) and alpha(2) helices, enabling a prolonged peptide-receptive conformation of the peptide binding cleft. Furthermore, analysis of H-2D(b) in complex with either m beta(2)m or h beta(2)m provides a structural explanation for the differential binding of H-2D(b)/h beta(2)m to both Ly49A and Ly49C. Our comparative structural study emphasizes the importance of beta(2)m residues at positions 3, 6 and 29 for binding to Ly49A and suggests that sterical hindrance by residue K6 on h beta(2)m impairs the recognition of Ly49C by H-2D(b)/gp33/h beta(2)m. Finally, comparison of the two H-2D(b) crystal structures implies that the beta(2)m species may affect the strength of TCR recognition by affecting CD8 binding. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:382 / 396
页数:15
相关论文
共 60 条
[1]   A structural basis for LCMV immune evasion:: Subversion of H-2Db and H-2Kb presentation of gp33 revealed by comparative crystal structure analyses [J].
Achour, A ;
Michaëlsson, J ;
Harris, RA ;
Odeberg, J ;
Grufman, P ;
Sandberg, JK ;
Levitsky, V ;
Kärre, K ;
Sandalova, T ;
Schneider, G .
IMMUNITY, 2002, 17 (06) :757-768
[2]   THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].
BAILEY, S .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763
[3]   BETA-2-MICROGLOBULIN FROM SERUM ASSOCIATES WITH MHC CLASS-I ANTIGENS ON THE SURFACE OF CULTURED-CELLS [J].
BERNABEU, C ;
VANDERIJN, M ;
LERCH, PG ;
TERHORST, CP .
NATURE, 1984, 308 (5960) :642-645
[4]   Role of CD8β domains in CD8 coreceptor function:: Importance for MHC I binding, signaling, and positive selection of CD8+ T cells in the thymus [J].
Bosselut, R ;
Kubo, S ;
Guinter, T ;
Kopacz, JL ;
Altman, JD ;
Feigenbaum, L ;
Singer, A .
IMMUNITY, 2000, 12 (04) :409-418
[5]   FREE R-VALUE - A NOVEL STATISTICAL QUANTITY FOR ASSESSING THE ACCURACY OF CRYSTAL-STRUCTURES [J].
BRUNGER, AT .
NATURE, 1992, 355 (6359) :472-475
[6]  
Brunger AT, 1998, ACTA CRYSTALLOGR D, V54, P905, DOI 10.1107/s0907444998003254
[7]   Mapping the ligand of the NK inhibitory receptor Ly49A on living cells [J].
Chung, DH ;
Natarajan, K ;
Boyd, LF ;
Tormo, J ;
Mariuzza, RA ;
Yokoyama, WM ;
Margulies, DH .
JOURNAL OF IMMUNOLOGY, 2000, 165 (12) :6922-6932
[8]   Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2Kb [J].
Dam, J ;
Guan, RJ ;
Natarajan, K ;
Dimasi, N ;
Chlewicki, LK ;
Kranz, DM ;
Schuck, P ;
Margulies, DH ;
Mariuzza, RA .
NATURE IMMUNOLOGY, 2003, 4 (12) :1213-1222
[9]   The complementarity-determining region-like loops of CD8α interact differently with β2-microglobulin of the class I molecules H-2Kb and thymic leukemia antigen, while similarly with their α3 domains [J].
Devine, L ;
Rogozinski, L ;
Naidenko, OV ;
Cheroutre, H ;
Kavathas, PB .
JOURNAL OF IMMUNOLOGY, 2002, 168 (08) :3881-3886
[10]  
ELLIOTT T, 1991, IMMUNOL TODAY, V12, P386