Structure and Function of NMDA Receptors
Structure and Function of NMDA Receptors
批准号:
9248017
负责人:
Vasanthi Jayaraman
金额:
$12.5万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-09-30 至 2019-08-31
关键词:
AddressAgonistAlzheimer&aposs DiseaseBindingC-terminalCationsCellsChemicalsCommunicationComplementComplexDataDiseaseElectrophysiology (science)ElectrostaticsExtracellular DomainFamilyFoundationsGlutamate ReceptorGlutamatesGlycineImageInvestigationIschemic StrokeLearningLengthLigand Binding DomainMapsMeasurementMediatingMediator of activation proteinMemoryMolecular ConformationMotionN-Methyl-D-Aspartate ReceptorsN-MethylaspartateNMDA receptor A1NeuraxisParkinson DiseasePathway interactionsPhysiological ProcessesProteinsPublishingRoentgen RaysRoleSchizophreniaSeizuresSignal PathwaySignal TransductionStrokeStructureSulfhydryl CompoundsSynaptic TransmissionTimeTranslatingcrosslinkdimerglutamatergic signalinginhibitor/antagonistinsightluminescence resonance energy transfermillisecondmolecular dynamicsmutantnervous system disorderpainful neuropathypublic health relevancereceptorreceptor functionsingle-molecule FRETtransmission process
中文摘要
英文摘要
DESCRIPTION (provided by applicant): N-methyl D-aspartate receptors are a subtype of glutamate receptors that mediate excitatory signal transmission in the mammalian central nervous system. Their primary function involves converting the chemical signal into an electrical signal, i.e. glutamate binding to an extracellular domain in the receptor triggers the formation of
cation permeable transmembrane channels in the receptor. Given the importance of these receptors in mediating a number of physiological processes and the need to modulate their function in disease states, the primary questions are how does the agonist activate the protein and how can this mechanism be modulated. The NMDA receptors are modulator in structure consisting of an amino terminal domain, agonist binding domain, channel segments and the C-terminal domains. Here we propose to study the communication between the domains and their role in dictating activation and allosteric modulation. Specifically we will investigate the role o the interactions between GluN1 agonist binding domain with the GluN2 subunit in controlling agonist binding domain dynamics and extent of activation (specific aim 1) using a combination of luminescence resonance energy transfer, smFRET, and electrophysiology. We will also investigate the pathway for allosteric modulation by establishing the conformational changes starting at the amino terminal domain through the agonist binding domain and study the changes in dynamics in the extracellular domains during the allosteric modulation (specific aim 2). The spectroscopic investigations will be complemented by electrophysiological measurements investigating the changes in function induced by alterations at the interface between the domains. These functional and structural investigations will provide a comprehensive understanding of the conformational pathway as well as role of dynamics in activation and allosteric modulation in NMDA receptor function.
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DOI:
10.1021/am403984k
发表时间:
2013-10-09
期刊:
ACS APPLIED MATERIALS & INTERFACES
影响因子:
9.5
作者:
[Chen, Jixin, Bremauntz, Alberto, Kisley, Lydia, Shuang, Bo, Landes, Christy F.]
通讯作者:
Landes, Christy F.
DOI:
10.1021/ac5039225
发表时间:
2015-01-06
期刊:
ANALYTICAL CHEMISTRY
影响因子:
7.4
作者:
[Kisley, Lydia, Landes, Christy F.]
通讯作者:
Landes, Christy F.
High ionic strength narrows the population of sites participating in protein ion-exchange adsorption: a single-molecule study.
高离子强度缩小了参与蛋白质离子交换吸附的位点数量:单分子研究。
DOI:
10.1016/j.chroma.2014.03.075
发表时间:
2014
期刊:
Journal of chromatography. A
影响因子:
--
作者:
[Kisley,Lydia, Chen,Jixin, Mansur,AndreaP, Dominguez-Medina,Sergio, Kulla,Eliona, Kang,MarciK, Shuang,Bo, Kourentzi,Katerina, Poongavanam,Mohan-Vivekanandan, Dhamane,Sagar, Willson,RichardC, Landes,ChristyF]
通讯作者:
Landes,ChristyF
DOI:
10.1002/jmr.2206
发表时间:
2012-08
期刊:
JOURNAL OF MOLECULAR RECOGNITION
影响因子:
2.7
作者:
[Daniels, Charlisa R., Kisley, Lydia, Kim, Hannah, Chen, Wen-Hsiang, Poongavanam, Mohan-Vivekanandan, Reznik, Carmen, Kourentzi, Katerina, Willson, Richard C., Landes, Christy F.]
通讯作者:
Landes, Christy F.
DOI:
10.1085/jgp.201411287
发表时间:
2014-12
期刊:
The Journal of general physiology
影响因子:
--
作者:
[MacLean DM, Ramaswamy SS, Du M, Howe JR, Jayaraman V]
通讯作者:
Jayaraman V
共 12 条
Dynamics Of Ligand Gated Ion Channels
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批准号:10330310
-
项目类别:
-
资助金额:$76.72万
-
财政年份:2017
-
负责人:Vasanthi Jayaraman
-
依托单位:
Dynamics Of Ligand Gated Ion Channels
-
批准号:10570200
-
项目类别:
-
资助金额:$67.78万
-
财政年份:2017
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负责人:Vasanthi Jayaraman
-
依托单位:
Dynamics of ligand gated ion channels
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批准号:9276535
-
项目类别:
-
资助金额:$23.01万
-
财政年份:2017
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负责人:Vasanthi Jayaraman
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依托单位:
TARP modulation of AMPA receptors
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批准号:8810076
-
项目类别:
-
资助金额:$30.81万
-
财政年份:2014
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负责人:Vasanthi Jayaraman
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依托单位:
TARP modulation of AMPA receptors
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批准号:8976615
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项目类别:
-
资助金额:$29.75万
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财政年份:2014
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负责人:Vasanthi Jayaraman
-
依托单位:
Structure and Function of NMDA Receptors
-
批准号:8665816
-
项目类别:
-
资助金额:$29.51万
-
财政年份:2011
-
负责人:Vasanthi Jayaraman
-
依托单位:
Structure and Function of NMDA Receptors
-
批准号:8474787
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项目类别:
-
资助金额:$28.48万
-
财政年份:2011
-
负责人:Vasanthi Jayaraman
-
依托单位:
Structure and Function of NMDA Receptors
-
批准号:8334656
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项目类别:
-
资助金额:$29.5万
-
财政年份:2011
-
负责人:Vasanthi Jayaraman
-
依托单位:
Structure and Function of NMDA Receptors
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批准号:8187924
-
项目类别:
-
资助金额:$33.24万
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财政年份:2011
-
负责人:Vasanthi Jayaraman
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依托单位:
Vibrational Spectroscopic Investigations of Glutamate Receptor
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批准号:7600442
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项目类别:
-
资助金额:$22.97万
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财政年份:2006
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负责人:Vasanthi Jayaraman
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依托单位:
Vibrational Spectroscopic Investigations of Glutamate Receptor
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批准号:7393691
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项目类别:
-
资助金额:$22.97万
-
财政年份:2006
-
负责人:Vasanthi Jayaraman
-
依托单位:
Vibrational Spectroscopic Investigations of Glutamate Receptor
-
批准号:7220653
-
项目类别:
-
资助金额:$22.97万
-
财政年份:2006
-
负责人:Vasanthi Jayaraman
-
依托单位:
Vibrational Spectroscopic Investigations of Glutamate Receptor
-
批准号:7798645
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项目类别:
-
资助金额:$22.74万
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财政年份:2006
-
负责人:Vasanthi Jayaraman
-
依托单位:
Spectroscopic Investigations of Glutamate Receptor
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批准号:7099158
-
项目类别:
-
资助金额:$23.66万
-
财政年份:2006
-
负责人:Vasanthi Jayaraman
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依托单位:
Subtype specific NMDA receptor antagonists
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批准号:6906171
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项目类别:
-
资助金额:$17.19万
-
财政年份:2005
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负责人:Vasanthi Jayaraman
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依托单位:
Subtype specific NMDA receptor antagonists
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批准号:7029712
-
项目类别:
-
资助金额:$16.77万
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财政年份:2005
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负责人:Vasanthi Jayaraman
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依托单位:
High throughout screening assay:glutamate receptor (RMI)
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批准号:6879390
-
项目类别:
-
资助金额:$7.3万
-
财政年份:2004
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负责人:Vasanthi Jayaraman
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依托单位:
国内基金
海外基金
Agonist-GPR119-Gs复合物的结构生物学研究
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批准号:32000851
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项目类别:青年科学基金项目
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资助金额:24.0万元
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批准年份:2020
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负责人:乔安娜
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依托单位: