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Direct protein-lipid interactions shape the conformational landscape of secondary transporters

Author

Listed:
  • Chloe Martens

    (Department of Chemistry, King’s College London, 7 Trinity Street)

  • Mrinal Shekhar

    (University of Illinois at Urbana-Champaign 405N. Mathews Ave.)

  • Antoni J. Borysik

    (Department of Chemistry, King’s College London, 7 Trinity Street)

  • Andy M. Lau

    (Department of Chemistry, King’s College London, 7 Trinity Street)

  • Eamonn Reading

    (Department of Chemistry, King’s College London, 7 Trinity Street)

  • Emad Tajkhorshid

    (University of Illinois at Urbana-Champaign 405N. Mathews Ave.)

  • Paula J. Booth

    (Department of Chemistry, King’s College London, 7 Trinity Street)

  • Argyris Politis

    (Department of Chemistry, King’s College London, 7 Trinity Street)

Abstract

Secondary transporters undergo structural rearrangements to catalyze substrate translocation across the cell membrane – yet how such conformational changes happen within a lipid environment remains poorly understood. Here, we combine hydrogen-deuterium exchange mass spectrometry (HDX-MS) with molecular dynamics (MD) simulations to understand how lipids regulate the conformational dynamics of secondary transporters at the molecular level. Using the homologous transporters XylE, LacY and GlpT from Escherichia coli as model systems, we discover that conserved networks of charged residues act as molecular switches that drive the conformational transition between different states. We reveal that these molecular switches are regulated by interactions with surrounding phospholipids and show that phosphatidylethanolamine interferes with the formation of the conserved networks and favors an inward-facing state. Overall, this work provides insights into the importance of lipids in shaping the conformational landscape of an important class of transporters.

Suggested Citation

  • Chloe Martens & Mrinal Shekhar & Antoni J. Borysik & Andy M. Lau & Eamonn Reading & Emad Tajkhorshid & Paula J. Booth & Argyris Politis, 2018. "Direct protein-lipid interactions shape the conformational landscape of secondary transporters," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06704-1
    DOI: 10.1038/s41467-018-06704-1
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    Cited by:

    1. Reza Dastvan & Ali Rasouli & Sepehr Dehghani-Ghahnaviyeh & Samantha Gies & Emad Tajkhorshid, 2022. "Proton-driven alternating access in a spinster lipid transporter," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Albert Suades & Aziz Qureshi & Sarah E. McComas & Mathieu Coinçon & Axel Rudling & Yurie Chatzikyriakidou & Michael Landreh & Jens Carlsson & David Drew, 2023. "Establishing mammalian GLUT kinetics and lipid composition influences in a reconstituted-liposome system," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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