Words similar to ras-related
Example sentences for: ras-related
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In all of the known Ras-related GTPases the guanine nucleotide binding site is surrounded by a set of highly conserved sequence elements [ 33 34 ] . One of these elements, termed the G2 motif, consists of NKxD (with the asparagine located at position 116 in H-Ras).
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.
Amino acid substitutions in the N(T)KxD motif cause a drastic reduction in the affinity of Ras-related GTPases for guanine nucleotides [ 35 36 ] . When overexpressed in cultured cells, these mutant GTPases function as dominant-suppressors of their endogenous counterparts [ 26 27 31 ] , presumably because they can compete for interaction with effectors, exchange factors or docking proteins, but cannot cycle on and off membranes in a nucleotide-dependent manner.
The addition of such tag sequences to Ras-related proteins, including several members of the Rab family, does not appear to alter their function or subcellular localization [ 36 37 38 ] .
Although the formation of intranuclear inclusions has not been observed in previous studies of Ras-related GTPases, it is a common feature of several neurodegenerative disorders where abnormal proteins containing poly-Gln tracts are synthesized as a result of CAG codon expansions [ 52 ] . Examples include Huntington's disease (huntingtin) [ 53 54 ] , spinocerebellar ataxia (SCA) types 1 and 3 (ataxin-1 and ataxin-3) [ 55 56 ] and dentatorubral-pallidoluysian atrophy (atrophin-1) [ 57 ] . These poly-Gln protein aggregates typically contain ubiquitin [ 58 ] and members of the Hsp70 chaperone family [ 59 ] , consistent with a proposed pathway for cellular clearance of toxic misfolded proteins.
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