Molecular Simulation and Biochemical Studies Support an Elevator-type Transport Mechanism in EIIC

Biophysical Journal
Jumin LeeWonpil Im

Abstract

Enzyme IIC (EIIC) is a membrane-embedded sugar transport protein that is part of the phosphoenolpyruvate-dependent phosphotransferases. Crystal structures of two members of the glucose EIIC superfamily, bcChbC in the inward-facing conformation and bcMalT in the outward-facing conformation, were previously solved. Comparing the two structures led us to the hypothesis that sugar translocation could be achieved by an elevator-type transport mechanism in which a transport domain binds to the substrate and, through rigid body motions, transports it across the membrane. To test this hypothesis and to obtain more accurate descriptions of alternate conformations of the two proteins, we first performed collective variable-based steered molecular dynamics (CVSMD) simulations starting with the two crystal structures embedded in model lipid bilayers, and steered their transport domain toward their own alternative conformation. Our simulations show that large rigid-body motions of the transport domain (55° in rotation and 8 Å in translation) lead to access of the substrate binding site to the alternate side of the membrane. H-bonding interactions between the sugar and the protein are intact, although the side chains of the binding-site resi...Continue Reading

References

Apr 26, 2005·Nucleic Acids Research·Yang Zhang, Jeffrey Skolnick
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Mar 21, 2008·Journal of Computational Chemistry·Sunhwan JoWonpil Im
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Feb 2, 2016·Nature Structural & Molecular Biology·Christopher MulliganJoseph A Mindell

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Citations

May 23, 2018·Proceedings of the National Academy of Sciences of the United States of America·Zhenning RenMing Zhou
Mar 19, 2019·Journal of Chemical Information and Modeling·Tomasz Pieńko, Joanna Trylska
Dec 8, 2021·Journal of Computational Chemistry·Abhishek A KognoleWonpil Im

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