Conformational Transition Pathways in Major Facilitator Superfamily Transporters

AbstractThe major facilitator superfamily (MFS) of transporters contains three classes of membrane transporters: symporters, uniporters, and antiporters. Despite utilizing a variety of transport methods, MFS transporters are believed to undergo similar con-formational changes within their distinct transport cycles. Although the similarities regarding conformational changes between the classes of MFS transporters are note-worthy, the differences are also valuable because they may explain the distinct functions of the classes within the MFS. Here, we have performed a variety of equilibrium and non-equilibrium all-atom molecular dynamics (MD) simulations of the bacterial proton-coupled oligopeptide transporter (GkPOT) and the human glucose transporter 1 (GluT1). To compare the similarities and differences of the conformational dynamics found within the three different classes of transporters we have also referenced previous simulations involving the glycerol-3-phosphate (GlpT) transporter. All of the proteins discussed here were simulated in the apo state in explicit membrane environments. Our results suggest a very similar conformational transition for all transporter types involving interbundle salt-bridge formation/disruption coupled with the orientation changes of transmembrane (TM) helices, specifically H1/H7 and H5/H11, resulting in an alternation in the accessibility of water at the cyto- and periplasmic gates.