Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent work on structural/functional relationships in arthropod proteasomes is reviewed. Taking advantage of our ability to induce a stable, proteolytically-active conformation of the lobster proteasome, the structures of basal and heat-activated complexes were probed with exogenous proteases. Increased sensitivity to chymotrypsin and trypsin showed that heat activation induced a more 'open' conformation, allowing entry of large substrates into the catalytic chamber. In Drosophila, the effects of two developmental mutant alleles (DTS-7 and DTS-5) encoding proteasome subunits (Z and C5, respectively) on the subunit composition and catalytic activities of the enzyme were examined. Both qualitative and quantitative differences in compositions between wild-type (+/+) and heterozygotes (+/DTS) indicated that incorporation of mutant subunits alters post-translational modifications of the complex. Catalytic activities, however, were similar, which suggests that the developmental defect involves other proteasome properties, such as intracellular localization and/or interactions with endogenous regulators. A hypothetical model in which DTS subunits act as poison subunits is presented.
 ...
PMID:Structure and functions of arthropod proteasomes. 1036 55

In Drosophila melanogaster the beta2 proteasome subunit gene, Prosbeta2, was first identified as a dominant temperature sensitive mutant, DTS-7, that causes pupal lethality at 29 degrees C but allows survival to adulthood at 25 degrees C. To explore the use of proteasome mutations for a conditional lethal system in insect pests, we identified and isolated the beta2 subunit gene of the 20S proteasome from the Caribbean fruit fly, Anastrepha suspensa. The caribfly ortholog AsProsbeta2 was isolated from pupal cDNA by 5' and 3' RACE. The AsProsbeta2 protein has high amino acid sequence similarity to predicted insect Prosbeta2 subunits and homologs from yeast and mammals, and it contains the well conserved amino acids that confer catalytic activity and substrate specificity. AsProsbeta2 is a single copy gene and its RNA accumulates throughout all developmental stages of the caribfly. For functional studies a point mutation, analogous to the Prosbeta2(1) mutation in D. melanogaster, was introduced into AsProsbeta2 to create an aberrant protein with a Gly170Arg substitution. Consistent with the DTS-7 mutation, transgenic insects carrying the mutant allele undergo normal metamorphosis at the permissive temperature (25 degrees C) but at the non-permissive temperature (29 degrees C) they exhibit effective pupal lethality. This is the first report of a functional characterization of a Prosbeta2 cognate based on the creation of a dominant temperature-sensitive mutation. This type of temperature-dependent lethality could be used for biological control, where transgenic insects are reared to adulthood at 25 degrees C or lower and then released into the field where ambient temperatures averaging 29 degrees C or greater cause lethality in their progeny.
 ...
PMID:Characterization of the proteasomebeta2 subunit gene and its mutant allele in the tephritid fruit fly pest, Anastrepha suspensa. 1952 65