Crystal structure and association behaviour of the GluR2 amino-terminal domain.
Fast excitatory neurotransmission is mediated largely by ionotropic glutamate receptors (iGluRs), tetrameric, ligand-gated ion channel proteins comprised of three subfamilies, AMPA, kainate and NMDA receptors, with each subfamily sharing a common, modular-domain architecture. For all receptor subfamilies, active channels are exclusively formed by assemblages of subunits within the same subfamily, a molecular process principally encoded by the amino-terminal domain (ATD). However, the molecular basis by which the ATD guides subfamily-specific receptor assembly is not known. Here we show that AMPA receptor GluR1- and GluR2-ATDs form tightly associated dimers and, by the analysis of crystal structures of the GluR2-ATD, propose mechanisms by which the ATD guides subfamily-specific receptor assembly.
Jin
Rongsheng
R
Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, CA, USA. rjin@burnham.org
Singh
Satinder K
SK
Gu
Shenyan
S
Furukawa
Hiroyasu
H
Sobolevsky
Alexander I
AI
Zhou
Jie
J
Jin
Yan
Y
Gouaux
Eric
E
D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry* / Q000378:metabolism*; D012996:Solutions
D000596:Amino Acids; D021122:Protein Subunits; D018091:Receptors, AMPA; D012996:Solutions; C104722:glutamate receptor ionotropic, AMPA 2