Structural mechanisms for gating of bacterial cyclic nucleotide-gated ion channels
Structural mechanisms for gating of bacterial cyclic nucleotide-gated ion channels
批准号:
10224689
负责人:
William N Zagotta
金额:
$39.64万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-20 至 2022-07-31
关键词:
AgonistArchitectureBindingBiochemicalBiological ModelsBrainCationsCryoelectron MicroscopyCyclic AMPCyclic GMPCyclic NucleotidesDataDetergentsElectronsEnvironmentEnzymesFreezingFunctional disorderGoalsHeartHeterogeneityIon ChannelKineticsLigandsLightLipidsMagnetic ResonanceMeasurementMeasuresMembrane LipidsMethodologyMethodsMicrofluidicsModelingMolecularMolecular ConformationMolecular MachinesNervous System PhysiologyNeuronsPacemakersPhotoreceptorsPhysiologicalPhysiologyPropertyProteinsPublishingResearch PersonnelResolutionRestSpectrum AnalysisSpin LabelsStructureSystemTestingbasecyclic-nucleotide gated ion channelsmolecular modelingnanodisknovelolfactory receptorreconstitutionresponse
中文摘要
环核苷酸调控的离子通道是精细的分子机器
英文摘要
Cyclic nucleotide-regulated ion channels are exquisite molecular machines that
underlie important physiological functions. Cyclic nucleotide-gated (CNG) channels
generate the primary electrical response to light in photoreceptors and to odorant in
olfactory receptors. The related hyperpolarization-activated cyclic nucleotide-gated
(HCN) channels underlie the pacemaker activity of the heart and many neurons in the
brain. These cation selective channels are opened by the direct binding of cyclic
nucleotides (cAMP and cGMP) to an intracellular domain of the channel. Our goal is to
reveal the molecular mechanism for this allostery in CNG channels. Our approach will
be to study bacterial CNG channels as a model system for the eukaryotic channels
because of the huge advantages they provide for our biochemical methods . We will
leverage the power of four different methodologies to determine the structure,
conformational heterogeneity, and dynamics of these channels: 1) cryoelectron
microscopy (cryo-EM), 2) double electron-electron resonance (DEER), 3) microfluidic
rapid freeze quench (µRFQ) in combination with DEER, and 4) Rosetta-based molecular
modeling. The proposal includes four investigators who are pioneers in each of these
methods. The use of all four methods on the same ion channel under the same
conditions is synergistic and ultimately will lead to a comprehensive structural and
energetic model for the allostery of this channel. Ultimately a molecular understanding
of these channels would inform not only the physiology and pathophysiology of the heart
and brain, but also the general mechanisms for allosteric control of many enzymes.
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Structural energetics of voltage- and ligand-dependent gating in ion channels
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批准号:10549486
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项目类别:
-
资助金额:$53.54万
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财政年份:2023
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负责人:William N Zagotta
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依托单位:
Functional and structural dynamics of KCNH4 and KCNH8
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批准号:10445688
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项目类别:
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资助金额:$15.55万
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财政年份:2022
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负责人:William N Zagotta
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依托单位:
Regulation of KCNH ion channels
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批准号:8758371
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项目类别:
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资助金额:$38.63万
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财政年份:2014
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负责人:William N Zagotta
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依托单位:
Molecular mechanisms for regulation of HCN channels by TRIP8b subunits
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批准号:8279160
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项目类别:
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资助金额:$23.4万
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财政年份:2011
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负责人:William N Zagotta
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依托单位:
Molecular mechanisms for regulation of HCN channels by TRIP8b subunits
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批准号:8092046
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项目类别:
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资助金额:$19.5万
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财政年份:2011
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负责人:William N Zagotta
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依托单位:
GATING MECHANISMS OF RETINAL ROD CGMP ACTIVATED CHANNELS
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批准号:6489805
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项目类别:
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资助金额:$16.56万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
GATING MECHANISMS OF RETINAL ROD CGMP-ACTIVATED CHANNELS
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批准号:2164130
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项目类别:
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资助金额:$14.78万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
GATING MECHANISMS OF RETINAL ROD cGMP ACTIVATED CHANNELS
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批准号:7004525
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项目类别:
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资助金额:$29.61万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
Gating Mechanisms of Retinal Rod cGMP Activated Channels
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批准号:8265002
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项目类别:
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资助金额:$33.36万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
Gating Mechanisms of Retinal Cyclic Nucleotide-Regulated Ion Channels
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批准号:10372190
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项目类别:
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资助金额:$37.71万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
GATING MECHANISMS OF RETINAL ROD CGMP ACTIVATED CHANNELS
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批准号:2765445
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项目类别:
-
资助金额:$14.97万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
GATING MECHANISMS OF RETINAL ROD CGMP ACTIVATED CHANNELS
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批准号:6342623
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项目类别:
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资助金额:$16.08万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
Gating Mechanisms of Retinal Rod cGMP Activated Channels
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批准号:8068798
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项目类别:
-
资助金额:$33.36万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
GATING MECHANISMS OF RETINAL ROD cGMP ACTIVATED CHANNELS
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批准号:7176759
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项目类别:
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资助金额:$29.44万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
Gating Mechanisms of Retinal Cyclic Nucleotide-Regulated Ion Channels
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批准号:9902455
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项目类别:
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资助金额:$38.88万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
Gating Mechanisms of Retinal Cyclic Nucleotide-Regulated Ion Channels
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批准号:10162596
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项目类别:
-
资助金额:$37.71万
-
财政年份:1994
-
负责人:William N Zagotta
-
依托单位:
GATING MECHANISMS OF RETINAL ROD CGMP-ACTIVATED CHANNELS
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批准号:2164132
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项目类别:
-
资助金额:$14.61万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
GATING MECHANISMS OF RETINAL ROD cGMP ACTIVATED CHANNELS
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批准号:6840784
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项目类别:
-
资助金额:$30.32万
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财政年份:1994
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负责人:William N Zagotta
-
依托单位:
GATING MECHANISMS OF RETINAL ROD CGMP-ACTIVATED CHANNELS
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批准号:2634432
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项目类别:
-
资助金额:$15.79万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
GATING MECHANISMS OF RETINAL ROD CGMP ACTIVATED CHANNELS
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批准号:6138171
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项目类别:
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资助金额:$15.62万
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财政年份:1994
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负责人:William N Zagotta
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依托单位:
海外基金