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Ras‐binding domains: predicting function versus folding
Author(s) -
Kalhammer Georg,
Bähler Martin,
Schmitz Frank,
Jöckel Johannes,
Block Christoph
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01076-4
Subject(s) - binding domain , gtpase , binding site , myr , effector , protein kinase domain , sh3 domain , computational biology , kinase , biology , plasma protein binding , folding (dsp implementation) , small gtpase , chemistry , microbiology and biotechnology , function (biology) , biophysics , biochemistry , signal transduction , gene , genome , proto oncogene tyrosine protein kinase src , engineering , mutant , electrical engineering
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.