1. Ras-binding domains: predicting function versus folding
- Author
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Christoph Block, Martin Bähler, Johannes Jöckel, Georg Kalhammer, and Frank Schmitz
- Subjects
Models, Molecular ,Protein Folding ,GTPase-activating protein ,Protein Conformation ,Diacylglycerol kinase ,Biophysics ,Computational biology ,Hybrid Cells ,Myosins ,Biology ,Unconventional myosin ,Biochemistry ,Protein structure ,Structural Biology ,Genetics ,Animals ,Binding site ,Molecular Biology ,Binding Sites ,Ras-effector ,Rho-GAP ,Effector ,Ras-binding domain ,myr ,Cell Biology ,Recombinant Proteins ,Rats ,Proto-Oncogene Proteins c-raf ,Myr 5 ,ras Proteins ,Protein folding ,Guanine nucleotide exchange factor ,Signal Transduction - Abstract
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.
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