An analysis of conformational changes on protein-protein association: implications for predictive docking

被引:172
作者
Betts, MJ [1 ]
Sternberg, MJE [1 ]
机构
[1] Imperial Canc Res Fund, Biomolec Modelling Lab, London WC2A 3PX, England
来源
PROTEIN ENGINEERING | 1999年 / 12卷 / 04期
关键词
protein conformational change; protein-protein docking;
D O I
10.1093/protein/12.4.271
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
Conformational changes on complex formation have been measured for 39 pairs of structures of complexed proteins and unbound equivalents, averaged over interface and non-interface regions and for individual residues. We evaluate their significance by comparison with the differences seen in 12 pairs of independently solved structures of identical proteins, and find that just over half have some substantial overall movement. Movements involve main chains as well as side chains, and large changes in the interface are closely involved with complex formation, while those of exposed non-interface residues are caused by flexibility and disorder Interface movements in enzymes are similar in extent to those of inhibitors. All eight of the complexes (six enzyme-inhibitor and two antibody-antigen) that have structures of both components in an unbound form available show some significant interface movement. However; predictive docking is successful even when some of the largest changes occur We note however that the situation may be different in systems other than the enzyme-inhibitors which dominate this study. Thus the general model is induced fit but, because there is only limited conformational change in many systems, recognition can be treated as lock and key to a first approximation.
引用
收藏
页码:271 / 283
页数:13
相关论文
共 38 条
  • [11] CRYSTAL-STRUCTURE ANALYSIS OF AMICYANIN AND APOAMICYANIN FROM PARACOCCUS-DENITRIFICANS AT 2.0-ANGSTROM AND 1.8-ANGSTROM RESOLUTION
    DURLEY, R
    CHEN, LY
    MATHEWS, FS
    DAVIDSON, VL
    [J]. PROTEIN SCIENCE, 1993, 2 (05) : 739 - 752
  • [12] COMPARISON OF CONFORMATIONAL CHARACTERISTICS IN STRUCTURALLY SIMILAR PROTEIN PAIRS
    FLORES, TP
    ORENGO, CA
    MOSS, DS
    THORNTON, JM
    [J]. PROTEIN SCIENCE, 1993, 2 (11) : 1811 - 1826
  • [13] Modelling protein docking using shape complementarity, electrostatics and biochemical information
    Gabb, HA
    Jackson, RM
    Sternberg, MJE
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1997, 272 (01) : 106 - 120
  • [14] STRUCTURAL MECHANISMS FOR DOMAIN MOVEMENTS IN PROTEINS
    GERSTEIN, M
    LESK, AM
    CHOTHIA, C
    [J]. BIOCHEMISTRY, 1994, 33 (22) : 6739 - 6749
  • [15] ANALYSIS OF PROTEIN LOOP CLOSURE - 2 TYPES OF HINGES PRODUCE ONE MOTION IN LACTATE-DEHYDROGENASE
    GERSTEIN, M
    CHOTHIA, C
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1991, 220 (01) : 133 - 149
  • [16] 3-DIMENSIONAL STRUCTURE OF THE COMPLEXES BETWEEN BOVINE CHYMOTRYPSINOGEN-A AND 2 RECOMBINANT VARIANTS OF HUMAN PANCREATIC SECRETORY TRYPSIN-INHIBITOR (KAZAL-TYPE)
    HECHT, HJ
    SZARDENINGS, M
    COLLINS, J
    SCHOMBURG, D
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1991, 220 (03) : 711 - 722
  • [17] 3-DIMENSIONAL STRUCTURE OF A RECOMBINANT VARIANT OF HUMAN PANCREATIC SECRETORY TRYPSIN-INHIBITOR (KAZAL TYPE)
    HECHT, HJ
    SZARDENINGS, M
    COLLINS, J
    SCHOMBURG, D
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1992, 225 (04) : 1095 - 1103
  • [18] CONFORMATIONAL FLEXIBILITY AND ITS FUNCTIONAL-SIGNIFICANCE IN SOME PROTEIN MOLECULES
    HUBER, R
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1979, 4 (12) : 271 - 276
  • [19] Rapid refinement of protein interfaces incorporating solvation: Application to the docking problem
    Jackson, RM
    Gabb, HA
    Sternberg, MJE
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1998, 276 (01) : 265 - 285
  • [20] JANIN J, 1990, J BIOL CHEM, V265, P16027