Words similar to gdp-bound
Example sentences for: gdp-bound
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Several laboratories have shown that in addition to mutations in the N(T)KxD motif, which reduce overall nucleotide binding, dominant-negative Rab constructs can be generated by introducing amino acid substitutions ( e.g. , asparagine) at the position cognate to Ras S17 ( i.e. , S22 in Rab24) [ 31 40 41 42 ] . Such proteins are thought to be locked in an inactive GDP-bound state because the mutation markedly reduces their affinity for GTP, compared to GDP [ 42 ] . As shown in Fig.
Rab proteins comprise a large family of Ras-related GTPases that function in the anterograde and retrograde trafficking of proteins in mammalian cells [ 1 2 3 ] . Different Rab proteins reside in specific subcellular membranes or organelles, where they mediate vesicular transport between discrete donor and acceptor compartments in the endocytic or exocytic pathways [ 4 5 ] . Detailed studies of a few Rab proteins ( e.g .; Rab1, Rab5 and Rab9) have led to a general model wherein Rab proteins are presumed to cycle on and off donor and acceptor membranes in connection with changes in their guanine nucleotide state [ 6 7 8 ] . In the active GTP-bound state, Rab proteins associate with budding transport vesicles [ 9 10 11 ] and appear to participate in the assembly of membrane docking complexes [ 12 13 14 ] . Following vesicle fusion with the acceptor compartment and GTP hydrolysis, the inactive GDP-bound Rab is extracted from the membrane by a carrier protein termed guanine nucleotide dissociation inhibitor (GDI) [ 15 16 17 ] . The GTPase can then re-enter the transport cycle through nucleotide exchange promoted by a specific exchange factor at the donor vesicle membrane [ 18 19 20 ] . In addition to changes in guanine nucleotide state, the posttranslational prenylation of Rab proteins plays an important role in the cycling mechanism.
Since neither Rab24(S22N) nor Rab24(S67Q) showed evidence of being locked in a GDP-bound state, it is unlikely that either would function as a dominant-negative.
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