Crystal structure of flavocetin-A, a platelet glycoprotein Ib-binding protein, reveals a novel cyclic tetramer of C-type lectin-like heterodimers

被引:90
作者
Fukuda, K
Mizuno, H [1 ]
Atoda, H
Morita, T
机构
[1] Natl Inst Agrobiol Resources, Dept Biotechnol, Tsukuba, Ibaraki 3058602, Japan
[2] Univ Tsukuba, Inst Appl Biochem, Tsukuba, Ibaraki 3058572, Japan
[3] Meiji Pharmaceut Univ, Dept Biochem, Tokyo 2048588, Japan
关键词
D O I
10.1021/bi992134z
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
Snake venom contains a number of the hemostatically active C-type lectin-like proteins, which affect the interaction between von Willebrand factor (vWF) and the platelet glycoprotein (GP) Ib or platelet receptor to inhibit/induce platelet activation. Flavocetin-A (FL-A) is a high-molecular mass C-type lectinlike protein (149 kDa) isolated from the habu snake venom. FL-A binds with high affinity to the platelet GP Ib alpha-subunit and functions as a strong inhibitor of vWF-dependent platelet aggregation. We have determined the X-ray crystal structure of FL-A and refined to 2.5 Angstrom resolution. This is a first elucidation of a three-dimensional structure of the platelet GP Ib-binding protein. The overall structure reveals that the molecule is a novel cyclic tetramer (alpha beta)(4) made up of four alpha beta-heterodimers related by a crystallographic 4-fold symmetry. The tetramerization is mediated by an interchain disulfide bridge between cysteine residues at the C-terminus of the alpha-subunit and at the N-terminus of the beta-subunit in the neighboring alpha beta-heterodimer. The high affinity of FL-A for the platelet GP Ib alpha-subunit could be explained by a cooperative-binding action through the multiple binding sites of the tetramer.
引用
收藏
页码:1915 / 1923
页数:9
相关论文
共 55 条
  • [1] Binding of a novel 50-kilodalton alboaggregin from Trimeresurus albolabris and related viper venom proteins to the platelet membrane glycoprotein Ib-IX-V complex. Effect on platelet aggregation and glycoprotein Ib-mediated platelet activation
    Andrews, RK
    Kroll, MH
    Ward, CM
    Rose, JW
    Scarborough, RM
    Smith, AI
    Lopez, JA
    Berndt, MC
    [J]. BIOCHEMISTRY, 1996, 35 (38) : 12629 - 12639
  • [2] PURIFICATION OF BOTROCETIN FROM BOTHROPS-JARARACA VENOM - ANALYSIS OF THE BOTROCETIN-MEDIATED INTERACTION BETWEEN VONWILLEBRAND-FACTOR AND THE HUMAN-PLATELET MEMBRANE GLYCOPROTEIN-IB-IX COMPLEX
    ANDREWS, RK
    BOOTH, WJ
    GORMAN, JJ
    CASTALDI, PA
    BERNDT, MC
    [J]. BIOCHEMISTRY, 1989, 28 (21) : 8317 - 8326
  • [3] Molecular mechanisms of platelet adhesion and activation
    Andrews, RK
    Lopez, JA
    Berndt, MC
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 1997, 29 (01) : 91 - 105
  • [4] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY
    BAILEY, S
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 : 760 - 763
  • [5] ALSCRIPT - A TOOL TO FORMAT MULTIPLE SEQUENCE ALIGNMENTS
    BARTON, GJ
    [J]. PROTEIN ENGINEERING, 1993, 6 (01): : 37 - 40
  • [6] 3D DOMAIN SWAPPING - A MECHANISM FOR OLIGOMER ASSEMBLY
    BENNETT, MJ
    SCHLUNEGGER, MP
    EISENBERG, D
    [J]. PROTEIN SCIENCE, 1995, 4 (12) : 2455 - 2468
  • [7] BOTROCETIN (VENOM COAGGLUTININ) - REACTION WITH A BROAD-SPECTRUM OF MULTIMERIC FORMS OF FACTOR-VIII MACROMOLECULAR COMPLEX
    BRINKHOUS, KM
    READ, MS
    FRICKE, WA
    WAGNER, RH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (05): : 1463 - 1466
  • [8] Brunger A.T., 1992, X-Plor Manual Version 3.1
  • [9] Free R value: Cross-validation in crystallography
    Brunger, AT
    [J]. MACROMOLECULAR CRYSTALLOGRAPHY, PT B, 1997, 277 : 366 - 396
  • [10] FUNCTIONAL AND SEQUENCE CHARACTERIZATION OF AGKICETIN, A NEW GLYCOPROTEIN IB ANTAGONIST ISOLATED FROM AGKISTRODON ACUTUS VENOM
    CHEN, YL
    TSAI, IH
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 210 (02) : 472 - 477