Extended Data Fig. 4: Comparison of TMD architecture with α1β2γ2 and α1β1γ2 GABAA receptor structures in detergent.
From: Cryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer
a–f, Superposition of subunit chains of α1β3γ2L GABAA receptor (grey) onto equivalent chains of α1β2γ2 GABAA receptor in DDM (conformation B; PDB ID: 6D6T) and the γ2 subunit of α1β2γ2 GABAA receptor (conformation A; PDB ID: 6D6U). R.m.s.d. values are for Cα atoms over the entire subunit. g, Overview of the TMD of α1β3γ2 in nanodisc. h–j, Superposition of TMD for α1β2γ2 GABAA receptor conformation A (h), conformation B (i), α1β1γ2 GABAA receptor (PDB ID: 6DW0; j) and the α1β3γ2–nanodisc complex (grey ribbon). Transmembrane helices of the γ2 subunit are labelled. The transmembrane helices of the γ2 show considerable distortion in detergent-bound complexes. M4 helices in α1 and γ2 subunits were not modelled in the α1β1γ2 GABAA receptor. k–n, Superposition of β− subunits reveals conformational differences of the γ2+ subunit (α1β3γ2–nanodisc complex in grey). Differences in distance (∆) between selected residue Cα atoms (spheres) are indicated by black lines. Disruption of the γ2 TMD induces substantial displacement of loop 7, loop 2 and the M2–M3 loop at the ECD–TMD interface in the detergent-bound α1β2γ2 structures (l, m), and to a lesser extent in α1β1γ2 GABAA receptor (n). o–r, Close-up view of M2 helices at the level of −2ʹ proline or alanine residues (Cα atoms shown as spheres) in nanodisc (o) and detergent-bound structures (p–r).
