Ras‐binding domains: predicting function versus folding

FEBS Letters

Jöckel, Johannes¹  Bähler, Martin²  Block, Christoph¹  Schmitz, Frank¹  Kalhammer, Georg² 

[1] Max-Planck-Institut für Molekulare Physiologie, Abt. Strukturelle Biologie, Postfach 10 26 64, D-44026 Dortmund, Germany;Adolf-Butenandt-Institut/Zellbiologie, Ludwig-Maximilians-Universität München, Schillerstr. 42, D-80336 München, Germany

关键词: Ras-binding domain;    Ras-effector;    Unconventional myosin;    Myr 5;    Rho-GAP;    Diacylglycerol kinase;    DAG;    diacylglycerol;    GAP;    GTPase activating protein;    GEF;    guanine nucleotide exchange factor;    GppNp;    guanylyl-5′-yl imidodiphosphate;    GST;    glutathione S-transferase;    RBD;    Ras binding domain;   

DOI  :  10.1016/S0014-5793(97)01076-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Ras interacts with a number of effector molecules to achieve its prolific signalling. Based on iterative sequence profile and motif searches of databases a novel family of Ras-binding domains was recently identified (Ponting and Benjamin, Trends Biochem. Sci. 21: 422–425, 1996). Among them the rat unconventional myosin and Rho-GTPase-activating protein myr 5 was predicted to contain a Ras-binding domain at its N-terminus. Here we report that direct binding experiments between the proposed Ras-binding domain of myr 5 and Ras failed to demonstrate any interaction. Molecular modelling suggests that this domain in myr 5 adopts a similar folding topology as the Ras-binding domain of Raf kinase. However, unlike the Ras-binding domain of Raf kinase, the myr 5 domain lacks the positive surface charges necessary for binding the negatively charged Ras contact site. This result exemplifies the functional diversity of similar structures and suggests that the identified Ras-binding motif does not reliably predict Ras-binding domains.

【 授权许可】

Unknown