Crystal structure of two CD46 domains reveals an extended measles virus-binding surface

被引:130
作者
Casasnovas, JM
Larvie, M
Stehle, T
机构
[1] Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Boston, MA 02114 USA
[3] Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden
[4] Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Cambridge, MA 02139 USA
[5] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA
关键词
CD46; measles virus; membrane cofactor protein; short consensus repeat; virus-receptor interaction;
D O I
10.1093/emboj/18.11.2911
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
Measles virus is a paramyxovirus which, like other members of the family such as respiratory syncytial virus, is a major cause of morbidity and mortality worldwide, The cell surface receptor for measles virus in humans is CD46, a complement cofactor. We report here the crystal structure at 3.1 Angstrom resolution of the measles virus-binding fragment of CD46. The structure reveals the architecture and spatial arrangement of two glycosylated short consensus repeats with a pronounced interdomain bend and some flexibility at the domain interface, Amino acids involved in measles virus binding define a large, glycan-free surface that extends from the top of the first to the bottom of the second repeat. The extended virus-binding surface of CD46 differs strikingly from those reported for the human virus receptor proteins CD4 and intercellular cell adhesion molecule-1 (ICAM-1), suggesting that the CD46 structure utilizes a novel mode of virus recognition, A highly hydrophobic and protruding loop at the base of the first repeat bears a critical virus-binding residue, thereby defining an important recognition epitope. Molecules that mimic the conformation of this loop potentially could be effective anti-viral agents by preventing binding of measles virus to CD46.
引用
收藏
页码:2911 / 2922
页数:12
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  • [1] ADAMS EM, 1991, J IMMUNOL, V147, P3005
  • [2] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY
    BAILEY, S
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 : 760 - 763
  • [3] SOLUTION STRUCTURE OF A PAIR OF COMPLEMENT MODULES BY NUCLEAR-MAGNETIC-RESONANCE
    BARLOW, PN
    STEINKASSERER, A
    NORMAN, DG
    KIEFFER, B
    WILES, AP
    SIM, RB
    CAMPBELL, ID
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1993, 232 (01) : 268 - 284
  • [4] The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand
    Bella, J
    Kolatkar, PR
    Marlor, CW
    Greve, JM
    Rossmann, MG
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) : 4140 - 4145
  • [5] Clinical coxsackievirus B isolates differ from laboratory strains in their interaction with two cell surface receptors
    Bergelson, JM
    Modlin, JF
    WielandAlter, W
    Cunningham, JA
    Crowell, RL
    Finberg, RW
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1997, 175 (03) : 697 - 700
  • [6] DECAY-ACCELERATING FACTOR (CD55), A GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED COMPLEMENT REGULATORY PROTEIN, IS A RECEPTOR FOR SEVERAL ECHOVIRUSES
    BERGELSON, JM
    CHAN, M
    SOLOMON, KR
    STJOHN, NF
    LIN, HM
    FINBERG, RW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (13) : 6245 - 6248
  • [7] Structure and distribution of modules in extracellular proteins
    Bork, P
    Downing, AK
    Kieffer, B
    Campbell, ID
    [J]. QUARTERLY REVIEWS OF BIOPHYSICS, 1996, 29 (02) : 119 - 167
  • [8] FREE R-VALUE - A NOVEL STATISTICAL QUANTITY FOR ASSESSING THE ACCURACY OF CRYSTAL-STRUCTURES
    BRUNGER, AT
    [J]. NATURE, 1992, 355 (6359) : 472 - 475
  • [9] CRYSTALLOGRAPHIC R-FACTOR REFINEMENT BY MOLECULAR-DYNAMICS
    BRUNGER, AT
    KURIYAN, J
    KARPLUS, M
    [J]. SCIENCE, 1987, 235 (4787) : 458 - 460
  • [10] Mapping of the primary binding site of measles virus to its receptor CD46
    Buchholz, CJ
    Koller, D
    Devaux, P
    Mumenthaler, C
    SchneiderSchaulies, J
    Braun, W
    Gerlier, D
    Cattaneo, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (35) : 22072 - 22079