WHAT IS THE STRUCTURAL CORRELATE OF INTRACELLULAR POLYGLUTAMINE TOXICITY?
WHAT IS THE STRUCTURAL CORRELATE OF INTRACELLULAR POLYGLUTAMINE TOXICITY?
批准号:
7954377
负责人:
CLARE A PETERS-LIBEU
金额:
$0.02万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-03-01 至 2010-02-28
关键词:
AntibodiesBindingBiologicalCell Culture TechniquesComplexComputer Retrieval of Information on Scientific Projects DatabaseDataDiseaseFundingGlutamineGrantInstitutionLengthMJD1 proteinMolecularMolecular ConformationN-terminalNerve DegenerationNeurodegenerative DisordersProteinsResearchResearch PersonnelResourcesSolutionsSourceStaining methodStainsStretchingToxic effectUnited States National Institutes of Healthbasehuman Huntingtin proteinpolyglutamineresearch studystructural biologysynchrotron radiation
中文摘要
这个子项目是众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Expanded polyglutamine (polyQ) stretches greater than 36-40 glutamines in length are the only common feature in twelve unrelated proteins that cause neurodegenerative disease. Evidence indicates that abnormally long polyQ stretches confer new toxic functions that may be associated with the presence of soluble monomeric or oligomeric forms of the polyQ-containing protein. Although it is known that these forms eventually aggregate, it is not which of the soluble species are toxic. Identification of these toxic species will be a major breakthough in understanding the biological basis of these neurodegenerative diseases. We plan to use SAXS to determine the molecular envelope and monomeric or oligomeric state of polyQ-containing proteins in complexes with Fabs that bind polyQ. To identify toxic species, the information from the SAXS experiments will be correlated with the ability of the antibody staining to predict degeneration of neurons in cell culture experiments. Our preliminary experiments with complexes of the 3B5H10 Fab, an Fab specific for disease-associated stretches of polyQ, and an N-terminal fragment of the huntingtin protein with a 39 glutamine repeat indicated that the purified complex was well-behaved in solution at concentrations of 1.5- 5 mg/ml with no signs of aggregation. Data from this study was used to obtain of the molecular envelope of the monomeric conformation of the huntingtin fragment in the complex. We plan to extend these experiments by using longer polyQ repeats in the huntingtin fragment as well as constructs of ataxin-3 with variable polyglutamine repeats. In addition, Fabs such as the MW1 Fab which may promote polyglutamine toxicity in cell culture will be studied. A polyQbinding Fab that is ineffective at predicting polyglutamine toxicity will be studied as a control.
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WHAT IS THE STRUCTURAL CORRELATE OF INTRACELLULAR POLYGLUTAMINE TOXICITY?
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批准号:8170053
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项目类别:
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资助金额:$0.03万
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财政年份:2010
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负责人:CLARE A PETERS-LIBEU
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依托单位:
THE STRUCTURE OF MODEL LIPOPROTEINS
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批准号:7954320
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项目类别:
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资助金额:$0.02万
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财政年份:2009
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负责人:CLARE A PETERS-LIBEU
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依托单位:
WHAT IS THE STRUCTURAL CORRELATE OF INTRACELLULAR POLYGLUTAMINE TOXICITY?
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批准号:7722038
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项目类别:
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资助金额:$0.08万
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财政年份:2008
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负责人:CLARE A PETERS-LIBEU
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依托单位:
THE STRUCTURE OF MODEL LIPOPROTEINS
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批准号:7721972
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项目类别:
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资助金额:$0.15万
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财政年份:2008
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负责人:CLARE A PETERS-LIBEU
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依托单位:
WHAT IS THE STRUCTURAL CORRELATE OF INTRACELLULAR POLYGLUTAMINE TOXICITY?
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批准号:7598298
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项目类别:
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资助金额:$0.02万
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财政年份:2007
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负责人:CLARE A PETERS-LIBEU
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依托单位:
SOLUTION STRUCTURE OF APOLIPOPROTEIN PHOSPHOLIPID COMPLEXES WITH DIFFERENT PHOSP
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批准号:7598207
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项目类别:
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资助金额:$0.06万
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财政年份:2007
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负责人:CLARE A PETERS-LIBEU
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THE STRUCTURE OF MODEL LIPOPROTEINS
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项目类别:
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资助金额:$0.06万
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财政年份:2007
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负责人:CLARE A PETERS-LIBEU
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依托单位:
THE STRUCTURE OF MODEL LIPOPROTEINS
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批准号:7370365
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项目类别:
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资助金额:$0.19万
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财政年份:2006
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负责人:CLARE A PETERS-LIBEU
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依托单位:
THE STRUCTURE OF MODEL LIPOPROTEINS
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项目类别:
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资助金额:$0.52万
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财政年份:2005
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负责人:CLARE A PETERS-LIBEU
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依托单位:
STRUCTURE OF BIOLOGICALLY ACTIVE APOE
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批准号:6978221
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项目类别:
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资助金额:$0.25万
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财政年份:2004
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负责人:CLARE A PETERS-LIBEU
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依托单位:
STRUCTURE OF MODEL LIPOPROTEINS
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批准号:6976257
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项目类别:
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资助金额:$0.29万
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财政年份:2004
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负责人:CLARE A PETERS-LIBEU
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依托单位:
STRUCTURE OF RECEPTOR-ASSOCIATED PROTEIN
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批准号:6978106
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项目类别:
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资助金额:$0.25万
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财政年份:2004
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负责人:CLARE A PETERS-LIBEU
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依托单位:
STRUCTURE OF APOE GLYCOSAMINOGLYCAN COMPLEXES
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批准号:6526635
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项目类别:
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资助金额:$5.01万
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财政年份:2002
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负责人:CLARE A PETERS-LIBEU
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依托单位:
STRUCTURE OF APOE GLYCOSAMINOGLYCAN COMPLEXES
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批准号:6402761
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项目类别:
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资助金额:$4.38万
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财政年份:2001
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负责人:CLARE A PETERS-LIBEU
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依托单位:
STRUCTURE OF APOE GLYCOSAMINOGLYCAN COMPLEXES
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批准号:6213386
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项目类别:
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资助金额:$3.92万
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财政年份:2000
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负责人:CLARE A PETERS-LIBEU
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依托单位:
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