Ras-associating (RA) domain QuickView

Description:: Ras proteins are signal-transducing GTPases that cycle between inactive GDP-bound and active GTP-bound forms. Ras is a prolific signalling moleculeinteracting with a spectrum of effector molecules and acting through more thanone signalling pathway. A domain of about 100 residues, termed RA forRalGDS/AF-6 or Ras-Associating, interacts with Ras and other small GTPases. Itoccurs in one or two copies in a variety of signalling molecules. It can befound associated with many other domains, such as PDZ, Dilute (DIL), GEF, myosin motor, IQ, C1, C2, protein kinase, VPS9 or sterile alpha motif (SAM).Structurally, the RA domain of RalGDS consists of a five-stranded mixed beta-sheet interrupted by a 12 residue alpha-helix and two additional small alpha-helices. The structure of the RA domain belongs to theubiquitin alpha/beta roll superfold and is similar to that of the RBD domainand the N-terminal third of the FERM domain. The RAdomain forms a homodimer where the interdimer surface is composed of twocysteines (Cys 2 in each monomer) forming an intermolecular disulfide bondand two interacting intermolecular antiparallel beta-sheets. The major interaction between Ras and RalGDS RA domain occurs between two antiparallel beta-strands: beta 2 of Ras and beta 2 of RA. This interaction occurs both at the backbone as well as the side chain level.