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    Understanding the Conformational Diversity of Proton-Coupled Oligopeptide Transporter (POT) Family

    Proton-coupled oligopeptide transporters (POTs) are members of the major facilitator superfamily (MFS) proteins involved in uptake of nutrients across of the cell membrane. These proteins undergo intrinsic conformational changes between outward-facing (OF), occluded (OC) and inward-facing (IF) states to transport substrate molecules. AtNRT1.1 is a plant nitrate (NO3 – ) transporter identified in Arabidopsis thaliana, belonging to the POT family. It shares close structural and functional homology to the bacterial di/tri-peptide transporter PepTSo. In our study, we investigated the functional mechanism of AtNRT1.1 and PepTSo. Both transporter protein crystal structures are obtained in the IF state and dynamics between functionally important intermediate states remains elusive. We performed all atom molecular dynamics simulations over microsecond timescales to explore the conformational landscape of AtNRT1.1 and PepTSo. Since the conformational changes of these proteins occur at large 16a Sunday, February 12, 2017 timescales, an adaptive sampling approach has been employed to efficiently sample the free energy landscapes. MD results reveal key gating residues that act as transition switches for intracellular and extracellular opening of the transporter. In AtNRT1.1, the residues Lys164-Tyr480 of helices 4 and 10 stabilize the OC state and helices 1 and 7 move ~15A˚ to reach the OF state. In PepTSo, Ser131-Tyr431 of helices 4 and 10 act as gating residues to stabilize the OC state while the OF state is obtained by breaking the interaction between Arg32-Asp316 of helices 1 and 7. Our finding sheds light on the conformational dynamics and functional mechanisms of AtNRT1.1 and PepTSo leading to better understanding of the role of hidden intermediate states in membrane transporters
    Balaji Selvam, Diwakar Shukla. Understanding the Conformational Diversity of Proton-Coupled Oligopeptide Transporter (POT) Family. Biophysical Society, Feb 11-15, 2017, New Orleans.

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