Towards prediction of cognate complexes between the WW domain and proline‐rich ligands

FEBS Letters

Sudol, Marius¹  Einbond, Aaron¹ 

[1] Department of Biochemistry, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6547, USA

关键词: Protein-protein interaction;    Proline-rich motif;    Viral-Gag;    Sodium channel;    Liddle's syndrome;    Interleukin receptor;    Serine/threonine kinases;    SCID;    severe combined immunodeficiency;    Muscular dystrophy;    ENaC;    epithelial sodium channel;    IL-2R;    Interleukin-2 receptor;    MAP kinase;    mitogen-activated protein kinase;    MAPKA2;    MAP kinase activated protein kinase;    P;    proline;    SH;    Src homology;    W;    tryptophan;    WBP;    WW domain-binding protein;    Y;    tyrosine;    YAP;    Yes-associated protein of 65 kDa;    X;    any amino acid;   

DOI  :  10.1016/0014-5793(96)00263-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The WW domain is a structured protein module found in a wide range of regulatory, cytoskeletal, and signaling molecules. Its ligands contain proline-rich sequences, some of which show a core consensus of XPPXY that is critical for binding. In order to gain a better understanding of the molecular and biological functions of WW domains, we decided to predict their cognate ligands by searching databases for proteins containing the XPPXY consensus. Using several axioms that take into account evolutionary conservation and functional similarity, we have identified four groups of proteins representing candidate ligands that signal through known or unknown WW domains. These include viral Gag proteins, sodium channels, interleukin receptors, and a subgroup of serine/threonine kinases. In addition, we proposed that dystrophin and β-dystroglycan bind through the WW-XPPXY link and that interference with this interaction could result in muscular dystrophy. Our study provides guidelines for experiments to probe the molecular and biological functions of the WW domain-ligand connection. Should these predictions be proven empirically, the results may have important ramifications for basic research and medicine.

【 授权许可】

Unknown