The AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) subfamily of iGluRs (ionotropic glutamate receptors) is essential for fast excitatory neurotransmission in the central nervous system. The malfunction of AMPARs (AMPA receptors) has been implicated in many neurological diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. The active channels of AMPARs and other iGluR subfamilies are tetramers formed exclusively by assembly of subunits within the same subfamily. It has been proposed that the assembly process is controlled mainly by the extracellular ATD (N-terminal domain) of iGluR. In addition, ATD has also been implicated in synaptogenesis, iGluR trafficking and trans-synaptic signalling, through unknown mechanisms. We report in the present study a 2.5 Å (1 Å=0.1 nm) resolution crystal structure of the ATD of GluA1. Comparative analyses of the structure of GluA1-ATD and other subunits sheds light on our understanding of how ATD drives subfamily-specific assembly of AMPARs. In addition, analysis of the crystal lattice of GluA1-ATD suggests a novel mechanism by which the ATD might participate in inter-tetramer AMPAR clustering, as well as in trans-synaptic protein–protein interactions.
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Research Article|
August 12 2011
Crystal structure of the glutamate receptor GluA1 N-terminal domain
Guorui Yao;
Guorui Yao
1
*Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China
†Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, U.S.A.
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Yinong Zong;
Yinong Zong
1
†Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, U.S.A.
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Shenyan Gu;
Shenyan Gu
†Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, U.S.A.
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Jie Zhou;
Jie Zhou
†Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, U.S.A.
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Huaxi Xu;
Huaxi Xu
*Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China
†Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, U.S.A.
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Irimpan I. Mathews;
Irimpan I. Mathews
‡Stanford Synchrotron Radiation Lightsource, 2575 Sand Hill Road, Menlo Park, CA 94025, U.S.A.
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Rongsheng Jin
Rongsheng Jin
2
†Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, U.S.A.
2To whom correspondence should be addressed (email rjin@sanfordburnham.org).
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Publisher: Portland Press Ltd
Received:
May 05 2011
Revision Received:
June 03 2011
Accepted:
June 06 2011
Accepted Manuscript online:
June 06 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 438 (2): 255–263.
Article history
Received:
May 05 2011
Revision Received:
June 03 2011
Accepted:
June 06 2011
Accepted Manuscript online:
June 06 2011
Citation
Guorui Yao, Yinong Zong, Shenyan Gu, Jie Zhou, Huaxi Xu, Irimpan I. Mathews, Rongsheng Jin; Crystal structure of the glutamate receptor GluA1 N-terminal domain. Biochem J 1 September 2011; 438 (2): 255–263. doi: https://doi.org/10.1042/BJ20110801
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