Structure and function of RLIP76 (RalBP1): an intersection point between Ras and Rho signalling.
RLIP76 (Ral-interacting protein of 76 kDa) [also known as RalBP1 (Ral-binding protein 1)] is an effector for the Ral family small GTPases. RLIP76 has been implicated in a number of cell processes, including receptor-mediated endocytosis, cell migration, mitochondrial division and metabolite transport. RLIP76 has two recognizable domains in the centre of the protein sequence: a GAP (GTPase-activating protein) domain for the Rho family G-proteins and an RBD (Ral-binding domain). The remainder of RLIP76 has no discernable homology with other proteins. The RBD forms a simple coiled-coil of two α-helices, which interacts with RalB by binding to both of the nucleotide-sensitive 'switch' regions. Both of these RLIP76 helices are involved in the interaction with Ral, but the interhelix loop is left free. This is the location of one of the two ATP-binding sites that have been identified in RLIP76 and suggests that Ral interaction would not prevent ATP binding. The structure of the RhoGAP-RBD dyad shows that the two domains are fixed in their orientation by a relatively rigid linker. This domain arrangement allows the two domains to engage Rho family and Ral small G-proteins simultaneously at the membrane. This suggests that RLIP76 is a node for Rho and Ras family signalling.
*Department of Biochemistry, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.
Helen R
HR
Mott
*Department of Biochemistry, 80 Tennis Court Road, Cambridge CB2 1GA, U.K.
Darerca
D
Owen
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D020690:GTPase-Activating Proteins / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D015398:Signal Transduction; D018631:ras Proteins / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology
D018528:ATP-Binding Cassette Transporters; D020690:GTPase-Activating Proteins; C095637:RALBP1 protein, human; D000255:Adenosine Triphosphate; D018631:ras Proteins; D020741:rho GTP-Binding Proteins