Solid State NMR Studies of Amyloid Proteins
Solid State NMR Studies of Amyloid Proteins
批准号:
9366854
负责人:
ROBERT Guy GRIFFIN
金额:
$305.77万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-08-01 至 2022-08-31
关键词:
2,4-DinitrophenolAlzheimer&aposs DiseaseAmyloidAmyloid FibrilsAmyloid ProteinsAmyloidosisBindingBiological ModelsBrainBrain DiseasesChemicalsComplexComputer softwareCryoelectron MicroscopyCrystallizationDataDepositionDetectionDevelopmentDiagnosisDialysis procedureDiseaseExhibitsGluesGoalsHumanHybridsHydrogen BondingIndividualInvestigationIonsIsotopesLabelLearningMagicMeasurementMeasuresMetalsMethodologyMethodsMindModelingMolecular ChaperonesMolecular ConformationMolecular StructureN-terminalPathologicPatientsPeptidesPeriodicityPhysiologic pulsePolymorphPrealbuminProteinsRelaxationReproducibilityResearchResolutionSamplingSecondary Protein StructureSeedsSeriesSignal TransductionSolventsSpectrum AnalysisStructureSystemTechniquesTissuesTorsionVariantVertebral columnWaterWidthamyloid peptideamyloid structureaqueousbasebeta-2 Microglobulincold temperatureexperimental studyfrontierimprovedinstrumentationmethod developmentmonomermutantnext generationpeptide structureprotein structuresimulationsolid state nuclear magnetic resonancetool
中文摘要
本文主要研究了魔角自旋(MAS)核磁共振的应用与发展
英文摘要
The proposed research focuses on the application and development of magic angle spinning (MAS) NMR
as a tool for structural investigations of amyloid peptides and proteins. The research covers four major
topics.
A. Structure of Amyloid Peptides and Proteins
(1) Aβ 1-42: We have recently recorded MAS spectra of Aβ1-42 that exhibit excellent resolution, a single
polymorph, and have obtained the initial atomic resolution structure of this toxic form of this
Alzheimer's protein. We plan to: (a) determine the structure of mutants for Aβ1-42 including a cryoEM
studies of the fibrils; (b) determine the conformation of the N-terminus and its interaction with Zn2+ the
chaperone Brichos that inhibits propagation of Aβ1-42 fibrils, and (c) seed fibrils with human AD brain
extracts to determine the pathologically important structure of Aβ1-42 and determine their structures
(2) Beta-2-microglobulin (β2m) and ΔN6-β2m: Assignments for these 99 AA and 93 AA ΔN6 variant
dialysis related amyloidosis (DRA) proteins are largely complete. In addition, we established that the
strands are PIR, and have obtained sufficient constraints to determine a preliminary structure. We plan
to complete the structure with additional distances and torsion angle measurements.
(3) Water layer in amyloid: We intend to determine the structure of the water bilayer in TTR105-115 fibrils
and in GNNQQNY crystals, which appear to be a common feature of amyloid fibrils and the “glue” that
binds protofibrils to form fibrils. 1H, 2H and 17O MAS experiments will be used in these studies. As part
of this effort we plan to develop new instrumentation and pulse sequences for observation of 17O
ultimately yielding 5D DNP enhanced e-/1H/17O/13C/15N correlation spectra.
B. NMR methods None of the above structural studies would be possible absent NMR methods to assign
spectra, measure distances and torsion angles, to enhance signal intensities, etc. We therefore plan
to continue the development of the methods essential for these structural investigations. PAR and
PAIN have been essential to MAS NMR structure determinations but they are semiquantitative
methods to measure 13C-13C and 13C-15N distances. Using SPINEVOLUTION and SIMPSON
software and experiments on model systems, we plan to develop these approaches into quantitative
distance measurement techniques. 1H detection will be integrated into these 2nd order dipolar
recoupling techniques for optimally efficient structural studies.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Q-band Upgrade to an X-band Pulsed EPR spectrometer
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批准号:10177244
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项目类别:
-
资助金额:$92.02万
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财政年份:2021
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Community Engagement
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批准号:10224252
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项目类别:
-
资助金额:$0.82万
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财政年份:2019
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负责人:ROBERT Guy GRIFFIN
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依托单位:
MIT/Harvard Center for Magnetic Resonance
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批准号:10224248
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项目类别:
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资助金额:$104.43万
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财政年份:2019
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Cryoprobe repairs and amplifier replacement for the 800 and 750 MHz spectrometers
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批准号:10400474
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项目类别:
-
资助金额:$8.27万
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财政年份:2019
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负责人:ROBERT Guy GRIFFIN
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依托单位:
TR&D 4 -- Advanced Magic Angle Spinning NMR methods
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批准号:10224251
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项目类别:
-
资助金额:$3.0万
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财政年份:2019
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Admin & Mgmt
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批准号:10224249
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项目类别:
-
资助金额:$95.0万
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财政年份:2019
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Solid State NMR Studies of Amyloid Proteins
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批准号:10446323
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项目类别:
-
资助金额:$70.95万
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财政年份:2017
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Solid State NMR Studies of Amyloid Proteins
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批准号:10687158
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项目类别:
-
资助金额:$70.85万
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财政年份:2017
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负责人:ROBERT Guy GRIFFIN
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依托单位:
U.S.-Canada Winter School on Biomolecular Solid State NMR
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批准号:9398504
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项目类别:
-
资助金额:$1.0万
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财政年份:2017
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Console for an 800/89 DNP Spectrometer
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批准号:8448486
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项目类别:
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资助金额:$53.9万
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财政年份:2013
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负责人:ROBERT Guy GRIFFIN
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依托单位:
3rd U.S.-Canada Winter School on Biomolecular Solid State NMR
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批准号:8459165
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项目类别:
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资助金额:$1.0万
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财政年份:2012
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负责人:ROBERT Guy GRIFFIN
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依托单位:
800 MHz Low Temperature Magic Angle Spinning NMR Probe.
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批准号:7794177
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项目类别:
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资助金额:$30.0万
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财政年份:2009
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负责人:ROBERT Guy GRIFFIN
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依托单位:
2nd U.S.-Canada Winter School on Biomolecular Solid State NMR
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批准号:7806213
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项目类别:
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资助金额:$0.5万
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财政年份:2009
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Acquisition of a 900 MHz NMR Spectrometer
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批准号:6548308
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项目类别:
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资助金额:$531.13万
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财政年份:2002
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Acquisition of a 900 MHz NMR Spectrometer
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批准号:7088731
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项目类别:
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资助金额:$36.06万
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财政年份:2002
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Acquisition of a 900 MHz NMR Spectrometer
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批准号:6604943
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项目类别:
-
资助金额:$34.38万
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财政年份:2002
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Acquisition of a 900 MHz NMR Spectrometer
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批准号:6901945
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项目类别:
-
资助金额:$36.05万
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财政年份:2002
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负责人:ROBERT Guy GRIFFIN
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依托单位:
Acquisition of a 900 MHz NMR Spectrometer
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批准号:6765165
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项目类别:
-
资助金额:$35.2万
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财政年份:2002
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负责人:ROBERT Guy GRIFFIN
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依托单位:
SOLID STATE NMR FOR AMYLOID STRUCTURE DETERMINATION
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批准号:6469200
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项目类别:
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资助金额:$21.7万
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财政年份:2001
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负责人:ROBERT Guy GRIFFIN
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依托单位:
SOLID STATE NMR FOR AMYLOID STRUCTURE DETERMINATION
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批准号:6345897
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项目类别:
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资助金额:$21.7万
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财政年份:2000
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负责人:ROBERT Guy GRIFFIN
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依托单位: