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bioRxiv · 10.1101/708289

Conformational Transition Pathways in Major Facilitator Superfamily Transporters

Ogden, D.·Immadisetty, K.·Moradi, M.
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Abstract

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.

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Ogden, D., Immadisetty, K., Moradi, M.. 2019-08-05. Conformational Transition Pathways in Major Facilitator Superfamily Transporters. https://doi.org/10.1101/708289

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