Structure and Dynamics of the Telomerase Ribonucleoprotein
Structure and Dynamics of the Telomerase Ribonucleoprotein
批准号:
10528468
负责人:
Michael D Stone
金额:
$35.69万
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-12-15 至 2024-11-30
关键词:
Active SitesAddressAdoptedArchitectureBindingBiochemicalBiochemistryBiological AssayBiological ModelsBiophysicsCatalysisCatalytic DomainCellsCharacteristicsChromosomesComplexCoupledCryoelectron MicroscopyDNADNA biosynthesisDataDefectDeteriorationDiagnosisDiseaseDrug TargetingEnzymesEventFluorescence Resonance Energy TransferG-QuartetsGenetic RecombinationGenomeGenome StabilityGoalsGrowthHumanKineticsLabelMalignant NeoplasmsMediatingMethodsMolecularMolecular ConformationMovementMutationN-terminalNucleoproteinsNucleotidesPathway interactionsPositioning AttributePremature aging syndromeProcessPropertyProtein DynamicsProtein SubunitsProteinsRNARNA-Directed DNA PolymeraseRegulationReportingResearchResolutionReverse TranscriptionRibonucleoproteinsSiteStructureTechniquesTelomeraseTelomerase RNA ComponentTelomere ShorteningTertiary Protein StructureTestingTetrahymenaTetrahymena thermophilaTherapeuticTissuesX-Ray Crystallographybiophysical techniquescell growthcofactordesigndetection methodenzyme modelexperimental studyflexibilityloss of functionnovelnovel strategiespolypeptidepreventprotein protein interactionrecruitrepairedscaffoldsingle moleculetelomere
中文摘要
项目总结
英文摘要
Project Summary
The telomerase ribonucleoprotein (RNP) is required for maintaining telomeres, the specialized nucleoprotein
structures that protect eukaryotic chromosome ends from aberrant processing and deleterious end-to-end fu-
sion events. Telomerase catalyzes processive extension of telomere DNA via a unique catalytic mechanism
that requires a strong functional interdependence of the telomerase RNA, telomerase reverse transcriptase
(TERT), and several additional protein subunits. The primary objective of this proposal is to elucidate how
conserved structural RNA and protein domains coordinate the processes of telomerase RNP assembly, cataly-
sis, and recruitment to telomeres. To address this goal, we will utilize a multi-faceted experimental strategy that
combines single-molecule biophysical techniques paired with computational, biochemical, and high-resolution
structural approaches. We will study human telomerase and the enzyme from the model system Tetrahymena
thermophila. In aim 1, we will employ biochemical structure probing, single-molecule Förster resonance energy
transfer (smFRET), and x-ray crystallography to analyze structural intermediate states adopted by telomerase
RNA and TERT during the RNP assembly pathway. In aim 2, we will use smFRET and a novel telomerase ac-
tivity detection method to investigate conformational dynamics of protein and RNA domains that drive telomer-
ase function. In aim 3, we will study the dynamic DNA handling properties of the telomerase enzyme. These
experiments will focus on the molecular mechanisms for telomerase recruitment to telomeres as well as under-
standing how the intrinsic folding properties of telomere DNA regulate telomerase catalysis.
期刊论文(27)
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Kinetic partitioning modulates human telomere DNA G-quadruplex structural polymorphism.
动力学分配调节人端粒DNA G-四链体结构多态性。
DOI:
10.1371/journal.pone.0083420
发表时间:
2013
期刊:
PloS one
影响因子:
3.7
作者:
[Long X, Stone MD]
通讯作者:
Stone MD
DOI:
10.1261/rna.079190.122
发表时间:
2023-03
期刊:
RNA (New York, N.Y.)
影响因子:
--
作者:
[]
通讯作者:
DOI:
10.1038/nsmb.3101
发表时间:
2015-11
期刊:
Nature structural & molecular biology
影响因子:
16.8
作者:
[Jansson LI, Akiyama BM, Ooms A, Lu C, Rubin SM, Stone MD]
通讯作者:
Stone MD
Coordinated DNA dynamics during the human telomerase catalytic cycle.
在人端粒酶催化循环中协调的DNA动力学。
DOI:
10.1038/ncomms5146
发表时间:
2014-06-13
期刊:
NATURE COMMUNICATIONS
影响因子:
16.6
作者:
[Parks, Joseph W., Stone, Michael D.]
通讯作者:
Stone, Michael D.
DOI:
10.1016/j.cbpa.2011.10.008
发表时间:
2011-12
期刊:
Current opinion in chemical biology
影响因子:
7.8
作者:
[Hengesbach M, Akiyama BM, Stone MD]
通讯作者:
Stone MD
共 20 条
Structure and dynamics of the Tetrahymena telomerase ribonucleoprotein
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批准号:8204457
-
项目类别:
-
资助金额:$29.16万
-
财政年份:2010
-
负责人:Michael D Stone
-
依托单位:
Structure and Dynamics of the Telomerase Ribonucleoprotein
-
批准号:10064020
-
项目类别:
-
资助金额:$35.69万
-
财政年份:2010
-
负责人:Michael D Stone
-
依托单位:
Structure and dynamics of the Tetrahymena telomerase ribonucleoprotein
-
批准号:8910228
-
项目类别:
-
资助金额:$2.5万
-
财政年份:2010
-
负责人:Michael D Stone
-
依托单位:
Structure and dynamics of the Tetrahymena telomerase ribonucleoprotein
-
批准号:8023853
-
项目类别:
-
资助金额:$29.26万
-
财政年份:2010
-
负责人:Michael D Stone
-
依托单位:
Structure and dynamics of the Tetrahymena telomerase ribonucleoprotein
-
批准号:8389648
-
项目类别:
-
资助金额:$28.03万
-
财政年份:2010
-
负责人:Michael D Stone
-
依托单位:
Structure and Dynamics of the Telomerase Ribonucleoprotein
-
批准号:10311529
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项目类别:
-
资助金额:$35.69万
-
财政年份:2010
-
负责人:Michael D Stone
-
依托单位:
Structure and Dynamics of the Telomerase Ribonucleoprotein
-
批准号:8962176
-
项目类别:
-
资助金额:$33.73万
-
财政年份:2010
-
负责人:Michael D Stone
-
依托单位:
Structure and dynamics of the Tetrahymena telomerase ribonucleoprotein
-
批准号:8586317
-
项目类别:
-
资助金额:$28.92万
-
财政年份:2010
-
负责人:Michael D Stone
-
依托单位:
海外基金