Fig. 10. Key residues involved in signal transduction through the CLR.

A. Residues involved in ECD/TMD cross-talk in the classical CLR. Alignment of the amino acid sequences of the β1-β2, β6-β7 (Cys-loop) and β8-β9 loops, the pre-M1/M1 segments and the M2-M3 linkers in ZAC, selected classical CLRs and the prokaryotic CLRs GLIC and ELIC. The conservation of key residues for the ECD/TMD cross-talk are indicated (negatively charged or charge-neutral, polar residues in red and positively charged residues blue, structural residues in green). B. Residues involved in orthosteric agonist binding to the classical CLR. Alignment of the amino acid sequences of loops A-F in ZAC and selected classical CLRs. The residues in the loops directly involved in orthosteric agonist binding to m5-HT₃AR [12], hα₄β₂ nAChR [14], hα₁β₂γ2 GABA_AR [13] and hα₁ GlyR [10] are indicated in bold and highlighted in yellow.