Recognition of proline-rich motifs by protein-protein-interaction domains

被引:206
作者
Ball, LJ
Kühne, R
Schneider-Mergener, J
Oschkinat, H
机构
[1] FMP, D-13125 Berlin, Germany
[2] Humboldt Univ, Charite, Inst Med Immunol, D-10115 Berlin, Germany
关键词
binding domains; molecular recognition; proline; protein folding; proteins;
D O I
10.1002/anie.200400618
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
(Chemical Equation Presented) Protein-protein interactions are essential in every aspect of cellular activity. Multiprotein complexes form and dissociate constantly in a specifically tuned manner, often by conserved mechanisms. Protein domains that bind proline-rich motifs (PRMs) are frequently involved in signaling events. The unique properties of proline provide a mechanism for highly discriminatory recognition without requiring high affinities. We present herein a detailed, quantitative assessment of the structural features that define the interfaces between PRM-binding domains and their target PRMs, and investigate the specificity of PRM recognition. Together with the analysis of peptide-library screens, this approach has allowed the identification of several highly conserved key interactions found in all complexes of PRM-binding domains. The inhibition of protein-protein interactions by using small-molecule agents is very challenging. Therefore, it is important to first pinpoint the critical interactions that must be considered in the design of inhibitors of PRM-binding domains. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.
引用
收藏
页码:2852 / 2869
页数:18
相关论文
共 116 条
  • [91] POLY(L-PROLINE)-BINDING PROTEINS FROM CHICK-EMBRYOS ARE A PROFILIN AND A PROFILACTIN
    TANAKA, M
    SHIBATA, H
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1985, 151 (02): : 291 - 297
  • [92] The crystal structure of a major allergen from plants
    Thorn, KS
    Christensen, HEM
    Shigeta, R
    Huddler, D
    Shalaby, L
    Lindberg, U
    Chua, NH
    Schutt, CE
    [J]. STRUCTURE, 1997, 5 (01) : 19 - 32
  • [93] Combining SPOT synthesis and native peptide ligation to create large arrays of WW protein domains
    Toepert, F
    Knaute, T
    Guffler, S
    Pirés, JR
    Matzdorf, T
    Oschkinat, H
    Schneider-Mergener, J
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (10) : 1136 - 1140
  • [94] Toepert F, 2001, ANGEW CHEM INT EDIT, V40, P897, DOI 10.1002/1521-3773(20010302)40:5<897::AID-ANIE897>3.0.CO
  • [95] 2-X
  • [96] TOEPERT F, 2001, ANGEW CHEM, V113, P922
  • [97] TOEPERT F, 2003, ANGEW CHEM, V115, P1168
  • [98] Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors
    Tu, JC
    Xiao, B
    Yuan, JP
    Lanahan, AA
    Leoffert, K
    Li, M
    Linden, DJ
    Worley, PF
    [J]. NEURON, 1998, 21 (04) : 717 - 726
  • [99] BASICITY DIFFERENCES AMONG PEPTIDE BONDS
    VEIS, A
    NAWROT, CF
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1970, 92 (13) : 3910 - &
  • [100] Structural basis for phosphoserine-proline recognition by group IVWW domains
    Verdecia, MA
    Bowman, ME
    Lu, KP
    Hunter, T
    Noel, JP
    [J]. NATURE STRUCTURAL BIOLOGY, 2000, 7 (08) : 639 - 643