Fig. 7. Proposed allosteric binding of fusidic acid to the transmembrane domain-binding pocket (TMD-BP) upon conformational changes of TM11/TM12 (magenta).

Concomitant cooperative binding of further fusidic acid (FUA) molecules (spheres) is indicated. Binding of FUA at the TMD-BP is suggested to facilitate H⁺-translocation in the T protomer transmembrane domain (TMD) triggering the T to O transition. Structural differences between the T protomer TMDs in T^PI and T^FI states are accompanied with changes in the PC1 and PC2 subdomains reflecting intermediate in-between T and O states (Supplementary Fig. 4d; Supplementary Note 3). PDB IDs of the displayed protomer structures: L, T, T^LIG-TM, O: 4DX5; T^PI, T^PI-LIG: 6ZOA; T^FI: 6ZOD. The ligands of T^LIG-TM, T^PI, T^PI-LIG1, are modelled and not part of the indicated PDB structures.