title: Ras-binding domains: predicting function versus folding.
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.
authors.affiliation: Adolf-Butenandt-Institut/Zellbiologie, Ludwig-Maximilians-Universität München, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kalhammer
authors.forename: M
authors.initials: M
authors.lastname: Bähler
authors.forename: F
authors.initials: F
authors.lastname: Schmitz
authors.forename: J
authors.initials: J
authors.lastname: Jöckel
authors.forename: C
authors.initials: C
authors.lastname: Block
mesh_terms: D000818:Animals; D001665:Binding Sites; D019852:Diacylglycerol Kinase / Q000737:chemistry / Q000378:metabolism; D006822:Hybrid Cells; D008958:Models, Molecular; D009218:Myosins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018631:ras Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C503808:Myo1e protein, rat; D011994:Recombinant Proteins; D019852:Diacylglycerol Kinase; D019908:Proto-Oncogene Proteins c-raf; D009218:Myosins; D018631:ras Proteins