ArticleBiophysical journal2006
Sugar binding and protein conformational changes in lactose permease.
Article in Biophysical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Structural and Functional Adaptability of Sucrose and Lactose Permeases fromBiochemistry · 2020Article
- Uptake dynamics in the Lactose permease (LacY) membrane protein transporter.Scientific reports · 2018Article
- Microscopic Characterization of Membrane Transporter Function by In Silico Modeling and Simulation.Methods in enzymology · 2016Review
- The Structure and Function of OxlT, the Oxalate Transporter of Oxalobacter formigenes.The Journal of membrane biology · 2015Review
- Flexible gates generate occluded intermediates in the transport cycle of LacY.Journal of molecular biology · 2014Article
- Protonation drives the conformational switch in the multidrug transporter LmrP.Nature chemical biology · 2014Article
- Structural basis for dynamic mechanism of proton-coupled symport by the peptide transporter POT.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Visualizing functional motions of membrane transporters with molecular dynamics simulations.Biochemistry · 2013Review
- Proton-coupled dynamics in lactose permease.Structure (London, England : 1993) · 2012Article
- Article
- Lactose permease and the alternating access mechanism.Biochemistry · 2011Article
- Probing the periplasmic-open state of lactose permease in response to sugar binding and proton translocation.Journal of molecular biology · 2010Article
- Article
- Identification of specific lipid-binding sites in integral membrane proteins.The Journal of biological chemistry · 2010Article
- Relating protein conformational changes to packing efficiency and disorder.Protein science : a publication of the Protein Society · 2009Article
- Molecular dynamics simulations of membrane channels and transporters.Current opinion in structural biology · 2009Review
- Identification of two distinct inactive conformations of the beta2-adrenergic receptor reconciles structural and biochemical observations.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Gating at both ends and breathing in the middle: conformational dynamics of TolC.Biophysical journal · 2008Article
- Using VMD: an introductory tutorial.Current protocols in bioinformatics · 2008Article
- Substrate binding and formation of an occluded state in the leucine transporter.Biophysical journal · 2008Article
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Authors and funding
4 authors.
Funding
Abstract
Lactose permease is an integral membrane protein that uses the cell membrane's proton gradient for import of lactose. Based on extensive biochemical data and a substrate-bound crystal structure, intermediates involved in lactose/H(+) co-transport have been suggested. Yet, the transport mechanism, especially the coupling of protonation states of essential residues and protein conformational changes involved in the transport, is not understood. Here we report molecular-dynamics simulations of membrane-embedded lactose permease in different protonation states, both in the presence and in the absence of lactose. The results analyzed in terms of pore diameter, salt-bridge formation, and substrate motion, strongly implicate Glu(269) as one of the main proton translocation sites, whose protonation state controls several key steps of the transport process. A critical ion pair (Glu(269) and Arg(144)) was found to keep the cytoplasmic entrance open, but via a different mechanism than the currently accepted model. After protonation of Glu(269), the salt bridge between Glu(269) and Arg(144) was found to break, and Arg(144) to move away from Glu(269), establishing a new salt bridge with Glu(126); furthermore, neutralization of Glu(269) and the displacement of Arg(144) and consequently of water molecules from the interdomain region was seen to initiate the closing of the cytoplasmic half channel (2.6-4.0 A reduction in diameter in the cytoplasmic constriction region in 10 ns) by allowing hydrophobic surfaces of the N- and C-domains to fuse. Charged Glu(269) was found to strongly bind the lactose permeant, indicating that proton transfer from water or another residue to Glu(269) is a prerequisite for unbinding of lactose from the binding pocket.
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