TY - JOUR
T1 - On the ion coupling mechanism of the MATE transporter ClbM
AU - Krah, Alexander
AU - Huber, Roland G.
AU - Zachariae, Ulrich
AU - Bond, Peter J.
N1 - Funding Information:
AK would like to thank Thomas Meier (Imperial College London) and Laura Preiss (Max Planck Institute of Biophysics) for helpful discussions. AK would also like to thank KIAS Center for Advanced Computation for providing computing resources.
Publisher Copyright:
© 2019 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Bacteria use a number of mechanisms to defend themselves from antimicrobial drugs. One important defense strategy is the ability to export drugs by multidrug transporters. One class of multidrug transporter, the so-called multidrug and toxic compound extrusion (MATE) transporters, extrude a variety of antibiotic compounds from the bacterial cytoplasm. These MATE transporters are driven by a Na+, H+, or combined Na+/H+ gradient, and act as antiporters to drive a conformational change in the transporter from the outward to the inward-facing conformation. In the inward-facing conformation, a chemical compound (drug) binds to the protein, resulting in a switch to the opposite conformation, thereby extruding the drug. Using molecular dynamics simulations, we now report the structural basis for Na+ and H+ binding in the dual ion coupled MATE transporter ClbM from Escherichia coli, which is connected to colibactin-induced genotoxicity, yielding novel insights into the ion/drug translocation mechanism of this bacterial transporter.
AB - Bacteria use a number of mechanisms to defend themselves from antimicrobial drugs. One important defense strategy is the ability to export drugs by multidrug transporters. One class of multidrug transporter, the so-called multidrug and toxic compound extrusion (MATE) transporters, extrude a variety of antibiotic compounds from the bacterial cytoplasm. These MATE transporters are driven by a Na+, H+, or combined Na+/H+ gradient, and act as antiporters to drive a conformational change in the transporter from the outward to the inward-facing conformation. In the inward-facing conformation, a chemical compound (drug) binds to the protein, resulting in a switch to the opposite conformation, thereby extruding the drug. Using molecular dynamics simulations, we now report the structural basis for Na+ and H+ binding in the dual ion coupled MATE transporter ClbM from Escherichia coli, which is connected to colibactin-induced genotoxicity, yielding novel insights into the ion/drug translocation mechanism of this bacterial transporter.
KW - MATE transporter
KW - MD simulations
KW - Ion-translocation mechanism
KW - Drug release mechanism
UR - http://www.scopus.com/inward/record.url?scp=85076456668&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2019.183137
DO - 10.1016/j.bbamem.2019.183137
M3 - Article
C2 - 31786188
SN - 0005-2736
VL - 1862
SP - 1
EP - 9
JO - BBA - Biomembranes
JF - BBA - Biomembranes
IS - 2
M1 - 183137
ER -