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Query: UMLS:C0271742 (AAA)
 3,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Escherichia coli sigma 32 transcriptional regulator has been shown to be degraded both in vivo and in vitro by the FtsH (HflB) protease, a member of the AAA protein family. In our attempts to study this process in detail, we found that two sigma 32 mutants lacking 15-20 C-terminal amino acids had substantially increased half-lives in vivo or in vitro, compared with wild-type sigma 32. A truncated version of sigma 32, sigma 32 C delta, was purified to homogeneity and shown to be resistant to FtsH-dependent degradation in vitro, suggesting that FtsH initiates sigma 32 degradation from its extreme C-terminal region. Purified sigma 32 C delta interacted with the DnaK and DnaJ chaperone proteins in a fashion similar to that of wild-type sigma 32. However, in contrast to wild-type sigma 32, sigma 32 C delta was largely deficient in its in vivo and in vitro interaction with core RNA polymerase. As a consequence, the truncated sigma 32 protein was completely non-functional in vivo, even when overproduced. Furthermore, it is shown that wild-type sigma 32 is protected from degradation by FtsH when complexed to the RNA polymerase core, but sensitive to proteolysis when in complex with the DnaK chaperone machine. Our results are in agreement with the proposal that the capacity of the DnaK chaperone machine to autoregulate its own synthesis negatively is simply the result of its ability to sequester sigma 32 from RNA polymerase, thus making it accessible to degradation by the FtsH protease.
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PMID:On the mechanism of FtsH-dependent degradation of the sigma 32 transcriptional regulator of Escherichia coli and the role of the Dnak chaperone machine. 998 18

Here we present the first description of the genomic organization, transcriptional regulatory sequences, and adult and embryonic gene expression for the mouse p97(CDC48) AAA ATPase. Clones representing two distinct p97 genes were isolated in a genomic library screen, one of them likely representing a non-functional processed pseudogene. The coding region of the gene encoding the functional mRNA is interrupted by 16 introns and encompasses 20.4 kilobase pairs. Definition of the transcriptional initiation site and sequence analysis showed that the gene contains a TATA-less, GC-rich promoter region with an initiator element spanning the transcription start site. Cis-acting elements necessary for basal transcription activity reside within 410 base pairs of the flanking region as determined by transient transfection assays. In immunohistological analyses, p97 was widely expressed in embryos and adults, but protein levels were tightly controlled in a cell type- and cell differentiation-dependent manner. A remarkable heterogeneity in p97 immunostaining was found on a cellular level within a given tissue, and protein amounts in the cytoplasm and nucleus varied widely, suggesting a highly regulated and intermittent function for p97. This study provides the basis for a detailed analysis of the complex regulation of p97 and the reagents required for assessing its functional significance using targeted gene manipulation in the mouse.
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PMID:The mouse p97 (CDC48) gene. Genomic structure, definition of transcriptional regulatory sequences, gene expression, and characterization of a pseudogene. 1018 99

The trans-translation system in bacteria promotes recycling of stalled ribosomes and targets incomplete peptides for proteolysis. In Escherichia coli, loss of trans-translation function has little effect on growth under normal laboratory conditions. Among the subtle phenotypes of tmRNA-deficient mutants is the inability to plate certain lambda imm(P22) phages. This phenotype is dependent on the ribosome recycling functions of the trans-translation system but is independent of its proteolysis-targeting activity. The experiments described here show that translation of the first (resume) codon of the tmRNA open reading frame by a tRNA is both necessary and sufficient for ribosome recycling. While a variety of sense codons can replace the naturally-occurring GCA alanine codon as the resume codon, both AAA and AAG lysine codons are non-functional resume codons. These results suggest that the main function of tmRNA in releasing stalled ribosomes is to supply a stop codon and so facilitate termination and subsequent ribosome recycling.
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PMID:Minimal translation of the tmRNA tag-coding region is required for ribosome release. 1741 10

Lon proteases are a family of ATP-dependent proteases involved in protein quality control, with a unique proteolytic domain and an AAA(+) (ATPases associated with various cellular activities) module accommodated within a single polypeptide chain. They were classified into two types as either the ubiquitous soluble LonA or membrane-inserted archaeal LonB. In addition to the energy-dependent forms, a number of medically and ecologically important groups of bacteria encode a third type of Lon-like proteins in which the conserved proteolytic domain is fused to a large N-terminal fragment lacking canonical AAA(+) motifs. Here we showed that these Lon-like proteases formed a clade distinct from LonA and LonB. Characterization of one such Lon-like protease from Meiothermus taiwanensis indicated that it formed a hexameric assembly with a hollow chamber similar to LonA/B. The enzyme was devoid of ATPase activity but retained an ability to bind symmetrically six nucleotides per hexamer; accordingly, structure-based alignment suggested possible existence of a non-functional AAA-like domain. The enzyme degraded unstructured or unfolded protein and peptide substrates, but not well-folded proteins, in ATP-independent manner. These results highlight a new type of Lon proteases that may be involved in breakdown of excessive damage or unfolded proteins during stress conditions without consumption of energy.
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PMID:A Lon-like protease with no ATP-powered unfolding activity. 2279 46

Chlorophyll biosynthesis is initiated by magnesium chelatase, an enzyme composed of three proteins, which catalyzes the insertion of Mg2+ into protoporphyrin IX to produce Mg-protoporphyrin IX. In barley (Hordeum vulgare L.) the three proteins are encoded by Xantha-f, Xantha-g and Xantha-h. Two of the gene products, XanH and XanG, belong to the structurally conserved family of AAA+ proteins (ATPases associated with various cellular activities) and form a complex involving six subunits of each protein. The complex functions as an ATP-fueled motor of the magnesium chelatase that uses XanF as substrate, which is the catalytic subunit responsible for the insertion of Mg2+ into protoporphyrin IX. Previous studies have shown that semi-dominant Xantha-h mutations result in non-functional XanH subunits that participate in the formation of inactive AAA complexes. In the present study, we identify severe mutations in the barley mutants xantha-h.38, -h.56 and -h.57. A truncated form of the protein is seen in xantha-h.38, whereas no XanH is detected in xantha-h.56 and -h.57. Heterozygous mutants show a reduction in chlorophyll content by 14-18% suggesting a slight semi-dominance of xantha-h.38, -h.56 and -h.57, which otherwise have been regarded as recessive mutations.
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PMID:Reduced chlorophyll biosynthesis in heterozygous barley magnesium chelatase mutants. 2460 74

Transfer messenger RNA (tmRNA; also known as 10Sa RNA or SsrA RNA) is a small RNA molecule that is conserved among bacteria. It has structural and functional similarities to tRNA: it has an upper half of the tRNA-like structure, its 5' end is processed by RNase P, it has typical tRNA-specific base modifications, it is aminoacylated with alanine, it binds to EF-Tu after aminoacylation and it enters the ribosome with EF-Tu and GTP. However, tmRNA lacks an anticodon, and instead it has a coding sequence for a short peptide called tag-peptide. An elaborate interplay of actions of tmRNA as both tRNA and mRNA with the help of a tmRNA-binding protein, SmpB, facilitates trans-translation, which produces a single polypeptide from two mRNA molecules. Initially alanyl-tmRNA in complex with EF-Tu and SmpB enters the vacant A-site of the stalled ribosome like aminoacyl-tRNA but without a codon-anticodon interaction, and subsequently truncated mRNA is replaced with the tag-encoding region of tmRNA. During these processes, not only tmRNA but also SmpB structurally and functionally mimics both tRNA and mRNA. Thus trans-translation rescues the stalled ribosome, thereby allowing recycling of the ribosome. Since the tag-peptide serves as a target of AAA(+) proteases, the trans-translation products are preferentially degraded so that they do not accumulate in the cell. Although alternative rescue systems have recently been revealed, trans-translation is the only system that universally exists in bacteria. Furthermore, it is unique in that it employs a small RNA and that it prevents accumulation of non-functional proteins from truncated mRNA in the cell. It might play the major role in rescuing the stalled translation in the bacterial cell.
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PMID:tmRNA-mediated trans-translation as the major ribosome rescue system in a bacterial cell. 2477 39