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Proton-coupled dynamics in lactose permease.

Magnus Andersson1, Ana-Nicoleta Bondar, J Alfredo Freites

  • 1Department of Physiology and Biophysics and Center for Biomembrane Systems, University of California at Irvine, Irvine, CA 92697-4560, USA.

Structure (London, England : 1993)
|September 25, 2012
PubMed
Summary

Molecular dynamics simulations reveal how lactose permease (LacY) transitions between inward and outward facing states. Deprotonation of a key residue, Glu325, triggers structural changes essential for H+ and sugar transport.

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Computational Biology

Background:

  • Lactose permease (LacY) in Escherichia coli facilitates the transport of lactose and protons across the cell membrane.
  • This transport occurs through an alternating access mechanism, involving conformational changes between inward- and outward-facing states.
  • Understanding these conformational dynamics is crucial for elucidating LacY's transport mechanism.

Purpose of the Study:

  • To investigate the early dynamics of the inward-to-outward conformational transition of lactose permease (LacY).
  • To explore the role of Glu325 protonation state and lipid environment in LacY's conformational changes using molecular dynamics simulations.

Main Methods:

  • Molecular dynamics (MD) simulations were performed on wild-type apo LacY.
  • Simulations were conducted in phosphatidylethanolamine (POPE) lipid bilayers with two protonation states of Glu325.
  • Additionally, simulations were performed in dipalmitoylphosphatidylcholine (DMPC) lipids to assess lipid dependence.

Main Results:

  • Deprotonation of Glu325 induced significant structural rearrangements in LacY.
  • These rearrangements brought critical side chains for proton and sugar binding into proximity and closed the internal cavity.
  • The dynamics of LacY were found to be dependent on the surrounding lipid environment (POPE vs. DMPC).

Conclusions:

  • The simulations provide atomic-level insights into the early stages of the LacY inward-to-outward transition.
  • Glu325 deprotonation is a key event driving the conformational change and preparing LacY for substrate release and proton translocation.
  • The findings align with experimental observations and highlight the importance of lipid-protein interactions in transporter function.