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Quantifying the stabilizing effects of protein–ligand interactions in the gas phase

Author

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  • Timothy M. Allison

    (University of Oxford)

  • Eamonn Reading

    (University of Oxford
    Present address: Department of Chemistry, Kings College London, Britannia House, 7 Trinity Street, London WC2R 2LS, UK)

  • Idlir Liko

    (University of Oxford)

  • Andrew J. Baldwin

    (University of Oxford)

  • Arthur Laganowsky

    (University of Oxford
    Present address: Department of Chemistry, Texas A&M University, Houston, Texas 77030, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Sciences Center, Houston, Texas 77030, USA)

  • Carol V. Robinson

    (University of Oxford)

Abstract

The effects of protein–ligand interactions on protein stability are typically monitored by a number of established solution-phase assays. Few translate readily to membrane proteins. We have developed an ion-mobility mass spectrometry approach, which discerns ligand binding to both soluble and membrane proteins directly via both changes in mass and ion mobility, and assesses the effects of these interactions on protein stability through measuring resistance to unfolding. Protein unfolding is induced through collisional activation, which causes changes in protein structure and consequently gas-phase mobility. This enables detailed characterization of the ligand-binding effects on the protein with unprecedented sensitivity. Here we describe the method and software required to extract from ion mobility data the parameters that enable a quantitative analysis of individual binding events. This methodology holds great promise for investigating biologically significant interactions between membrane proteins and both drugs and lipids that are recalcitrant to characterization by other means.

Suggested Citation

  • Timothy M. Allison & Eamonn Reading & Idlir Liko & Andrew J. Baldwin & Arthur Laganowsky & Carol V. Robinson, 2015. "Quantifying the stabilizing effects of protein–ligand interactions in the gas phase," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9551
    DOI: 10.1038/ncomms9551
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    Cited by:

    1. Tianqi Zhang & Jixing Lyu & Bowei Yang & Sangho D. Yun & Elena Scott & Minglei Zhao & Arthur Laganowsky, 2024. "Native mass spectrometry and structural studies reveal modulation of MsbA–nucleotide interactions by lipids," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Dilraj Lama & Thibault Vosselman & Cagla Sahin & Judit Liaño-Pons & Carmine P. Cerrato & Lennart Nilsson & Kaare Teilum & David P. Lane & Michael Landreh & Marie Arsenian Henriksson, 2024. "A druggable conformational switch in the c-MYC transactivation domain," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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