期刊
SCIENCE
卷 345, 期 6200, 页码 1021-1026出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1258409
关键词
-
资金
- American Heart Association [13POST13960004]
- Long-Term Fellowship of European Molecular Biology Organization
- institutional National Research Service Award (NRSA)
- NRSA [F32MH100331]
- NIH
AMPA-sensitive glutamate receptors are crucial to the structural and dynamic properties of the brain, to the development and function of the central nervous system, and to the treatment of neurological conditions from depression to cognitive impairment. However, the molecular principles underlying AMPA receptor activation have remained elusive. We determined multiple x-ray crystal structures of the GluA2 AMPA receptor in complex with a Conus striatus cone snail toxin, a positive allosteric modulator, and orthosteric agonists, at 3.8 to 4.1 angstrom resolution. We show how the toxin acts like a straightjacket on the ligand-binding domain (LBD) gating ring, restraining the domains via both intra-and interdimer cross-links such that agonist-induced closure of the LBD clamshells is transduced into an irislike expansion of the gating ring. By structural analysis of activation-enhancing mutants, we show how the expansion of the LBD gating ring results in pulling forces on the M3 helices that, in turn, are coupled to ion channel gating.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据