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Structural mechanism of glutamate receptor activation and desensitization.
Meyerson, Joel R; Kumar, Janesh; Chittori, Sagar; Rao, Prashant; Pierson, Jason; Bartesaghi, Alberto; Mayer, Mark L; Subramaniam, Sriram.
Afiliação
  • Meyerson JR; Laboratory of Cell Biology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland 20892, USA.
  • Kumar J; Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, NICHD, NIH, Bethesda, Maryland 20892, USA.
  • Chittori S; Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, NICHD, NIH, Bethesda, Maryland 20892, USA.
  • Rao P; Laboratory of Cell Biology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland 20892, USA.
  • Pierson J; FEI Company, Hillsboro, Oregon 97124, USA.
  • Bartesaghi A; Laboratory of Cell Biology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland 20892, USA.
  • Mayer ML; Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, NICHD, NIH, Bethesda, Maryland 20892, USA.
  • Subramaniam S; Laboratory of Cell Biology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland 20892, USA.
Nature ; 514(7522): 328-34, 2014 Oct 16.
Article em En | MEDLINE | ID: mdl-25119039
Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To gain a better understanding of how structural changes gate ion flux across the membrane, we trapped rat AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptor subtypes in their major functional states and analysed the resulting structures using cryo-electron microscopy. We show that transition to the active state involves a 'corkscrew' motion of the receptor assembly, driven by closure of the ligand-binding domain. Desensitization is accompanied by disruption of the amino-terminal domain tetramer in AMPA, but not kainate, receptors with a two-fold to four-fold symmetry transition in the ligand-binding domains in both subtypes. The 7.6 Å structure of a desensitized kainate receptor shows how these changes accommodate channel closing. These findings integrate previous physiological, biochemical and structural analyses of glutamate receptors and provide a molecular explanation for key steps in receptor gating.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Ácido Caínico / Receptores de AMPA / Microscopia Crioeletrônica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nature Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Ácido Caínico / Receptores de AMPA / Microscopia Crioeletrônica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nature Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos