Unusual basis of tRNA identity in human mitochondria
人类线粒体中 tRNA 身份的不寻常基础
基本信息
- 批准号:7455471
- 负责人:
- 金额:$ 1.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-03-01 至 2011-02-28
- 项目状态:已结题
- 来源:
- 关键词:AlanineAlanine-Specific tRNAAlanine-tRNA LigaseAmino AcidsAmino Acyl-tRNA SynthetasesAminoacylationAnimalsAntibioticsBacteriaBe++ elementBerylliumBiological AssayC-terminalChargeClassDefectDevelopmentElementsEnzymesEukaryotaEukaryotic CellEvolutionFacility Construction Funding CategoryFamilyHomologous GeneHumanHybridsIndividualKineticsLeadLigaseMapsMeasuresMitochondriaMitochondrial DiseasesMutagenesisMutationNucleotidesOrganismPeptidesPersonal SatisfactionPreparationPropertyProtein RegionProteinsRNARNA BindingRNA Recognition MotifRateResearchResearch PersonnelRoleSequence AlignmentSideSiteSite-Directed MutagenesisSourceSpecificityStructureSubstrate SpecificitySystemTestingTransfer RNAWorkbasedeletion analysisinterestmutantnovelnucleotide analogprogramsresearch studyspecies differencestemtRNA-alanine complex
项目摘要
PROJECT SUMMARY. Metazoan mitochondria contain tRNAs which are highly diverged in both
sequence and structure from those found elsewhere in evolution. These tRNAs are recognized and
specifically charged with their cognate amino acids by nuclearly encoded mitochondrial aminoacyl-tRNA
synthetases. Although the enzymes have a high degree of sequence similarity to cytoplasmic and bacterial
counterparts, examination of their unusual tRNA substrates suggests that novel modes of specific RNA
recognition may be employed. Metazoan mitochondrial alanyl-tRNA sythetases (AlaRSs) are of special
interest because the tRNA acceptor stem sequence that defines alanine identity in all other systems is
extremely variable in animal mitochondria.
The objective of the research proposed here is to elucidate the specific adaptations of human
mitochondrial AlaRS that allow this enzyme to recognize its bizarre tRNA substrate. Our preliminary results
show RNA recognition properties of previously characterized homologues from bacteria, eukaryotes and
other metazoan mitochondria poorly predict those of the human mitochondrial enzyme.
The basis of substrate specificity in the human mitochondrial system will be determined by mapping tRNA
identity elements using three approaches: construction of hybrid tRNAs, cross-species aminoacylation of
other animal mitochondrial tRNAs, and nucleotide analog interference mapping. These experiments will
guide the preparation of mutants to assess the importance of individual nucleotides.
The research will also determine the adaptations in the mitochondrial enzyme responsible for altered
specificity using deletion analysis to establish which of the conserved RNA binding domains of the protein
are involved in specific recognition. Site-directed mutation and domain swaps will be used to examine the
roles of specific side chains or peptides.
RELEVANCE. Because aminoacyl-tRNA synthetases are an essential family of enzymes with cross-
species differences in specificity, they make attractive targets for antibiotic development. Defects in aaRS
recognition of tRNA are also involved in several inheritible mitochondrial diseases. This work will extend our
basic understanding of the evolution and specificity of this important enzyme class, an understanding that is
vital to the continuing development of health-related applications.
项目总结。后生动物线粒体中含有trna,两者高度分化
项目成果
期刊论文数量(0)
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会议论文数量(0)
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JOSEPH W CHIHADE其他文献
JOSEPH W CHIHADE的其他文献
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{{ truncateString('JOSEPH W CHIHADE', 18)}}的其他基金
Unusual basis of tRNA identity in human mitochondria
人类线粒体中 tRNA 身份的不寻常基础
- 批准号:
7013010 - 财政年份:2006
- 资助金额:
$ 1.45万 - 项目类别: