Native ion mobility mass spectrometry (IM-MS) is an emerging biophysical technique to probes membrane protein complexes and their interactions with lipids and other molecules. Our recent work using native IM-MS to determine thermodynamics of individual ligand binding events to proteins highlights the powerful utility of this technique. Notably, thermodynamic parameters obtained using native IM-MS are in agreement with measurements from isothermal titration calorimetry and surface plasmon resonance. We also developed native IM-MS approaches to determine how individual lipid-binding events to membrane proteins can allosterically modulate their interactions with proteins and lipids. From these studies, we uncover that that lipid chain length and stereochemistry can affect the degree of allosteric modulation, indicating an unforeseen selectivity of membrane proteins toward the chemistry of lipid tails. Lastly, native IM-MS captures direct binding events of lipids and a toxin to a mammalian G-protein gated inward rectifying potassium channel. Adducts bound to the tetrameric channel as small as 80 Da can readily be resolved. In summary, native IM-MS is a powerful technique to probe very challenging questions in the chemistry of membrane protein interactions with lipids and other molecules.

Native ion mobility mass spectrometry of membrane protein complexes

2019 Spring National Meeting

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