In order to induce such a relative movement between TMs 4 and 10, the substrate binding signal must be transduced from the porter layer to the TM layer.
Thus, for an effective AcrB-like transporter, a mechanism of transducing the PMF energy into mechanical rearrangements in the porter layer likely exists.
Taken together, we proposed that the signaling motifs, especially that of PC1-CTM, are essential for transducing substrate binding signal from the porter layer to TM layer.
In the AcrB trimer, a differentially phased tilting process of the TM domains is likely to correlate with the packing rearrangement inside the porter layer.
During the B-E transition, PC1 exhibits the largest movement, compared to other subdomains in the porter layer (Seeger et al. 2006).
One important mechanistic question to address for RND transporters then is how substrate binding in the porter layer induces proton transport in the TM layer, which in turn is required to drive the transport of substrate across the outer membrane.
We proposed that this β-sheet provides an information path for the substrate binding signal transduced from the porter layer to the TM layer, and therefore we term this sheet PC1-CTM signaling motif.
An AcrB inhibitor that binds between PN2 and PC1 in the B-state seems to block this movement of PC1 (Nakashima et al. 2013), thus breaking the communication between the porter and TM layers.
The two functionally distinct domains are connected through four β-strands, which are involved in β-sheet formation at the interface between the porter- and TM-layers.
The AcrB trimer consists of three layers, namely transmembrane (TM) layer, porter layer, and adaptor-docking layer (Fig. 1).
