The Relative Orientation of the TM3 and TM4 Domains Varies between alpha 1 and alpha 3 Glycine Receptors

作者：Han Lu; Talwar Sahil; Lynch Joseph W^*

来源：ACS Chemical Neuroscience, 2013, 4(2): 248-254.

DOI：10.1021/cn300177g

• Binding site
• pLGIC
• Cys-loop receptor
• voltage clamp
• fluorescence
• mutagenesis

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 alpha 1 and alpha 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 alpha 1 and alpha 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 alpha 1 and alpha 3 GlyR TM4 domains are orientated differently relative to their TM3 domains. This may underlie their differential ability to influence glycine efficacy.

• 出版日期2013-2