The Relative Orientation of the TM3 and TM4 Domains Varies between 伪1 and 伪3 Glycine Receptors
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- 作者：Lu Han ; Sahil Talwar ; Joseph W. Lynch
- 刊名：ACS Chemical Neuroscience
- 出版年：2013
- 出版时间：February 20, 2013
- 年：2013
- 卷：4
- 期：2
- 页码：248-254
- 全文大小：311K
- 年卷期：v.4,no.2(February 20, 2013)
- ISSN：1948-7193
文摘
Glycine receptors (GlyRs) are anion-conducting members of the pentameric ligand-gated ion channel family. We previously showed that the dramatic difference in glycine efficacies of 伪1 and 伪3 GlyRs is largely attributable to their nonconserved TM4 domains. Because mutation of individual nonconserved TM4 residues had little effect, we concluded that the efficacy difference was a distributed effect of all nonconserved TM4 residues. We therefore hypothesized that the TM4 domains of 伪1 and 伪3 GlyRs differ in structure, membrane orientation, and/or molecular dynamic properties. Here we employed voltage-clamp fluorometry to test whether their TM4 domains interact differently with their respective TM3 domains. We found a rhodamine fluorophore covalently attached to a homologous TM4 residue in each receptor interacts differentially with a conserved TM3 residue. We conclude that the 伪1 and 伪3 GlyR TM4 domains are orientated differently relative to their TM3 domains. This may underlie their differential ability to influence glycine efficacy.