Defining state-selective lipid binding to brain GPCRs - introducing REVEAL
Lawrence, S. A. S.; Kirschbaum, C.; Lutomski, C. A.; Song, H.; Hinkle, J. D.; Butroid, F. I.; Melani, R.; Syka, J. E. P.; Mullen, C.; El-Baba, T. J.; Robinson, C. V.
Show abstract
Membrane lipids are central regulators of G protein-coupled receptor (GPCR) function. Defining receptor-specific lipid interactions in native, fully modified mammalian systems remains challenging. Extensive post-translational modifications generate heterogeneous proteoforms that confound conventional mass spectrometry approaches. Here we introduce REVEAL (REceptor enVironment Elucidation by Activated Lipid-release), an automated native top-down mass spectrometry strategy that discriminates specifically bound lipids from background. Applied here to intact, heterogeneous mammalian membrane protein complexes, incubated with a brain polar lipid extract (>1000 components), we define receptor-specific lipid-binding for two neuronal class C GPCRs. We show that agonism remodels lipid occupancy, selectively enriching a reduced repertoire of bound lipids. Plasmalogen lipids emerge as persistent binders across all conformational states of the metabotropic glycine receptor and are preferentially depleted under oxidative stress, implying a protective role at the receptor surface. These findings position lipids as dynamic regulators of both function and response to the cellular redox environment.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Data-independent acquisition method for ubiquitinome analysis reveals regulation of circadian biology 94%
- Surfaceome dynamics during neuronal development and synaptic plasticity reveal system-wide surfaceome reorganization independent of global proteostasis 94%
- DeFrND: detergent-free reconstitution into native nanodiscs with designer membrane scaffold peptides 94%
Similar papers in this journal
Similar papers in this journal
- Targeted Protein Acetylation in Cells Using Heterobifunctional Molecules 94%
- Chemical proteomics reveals regulation of bile salt hydrolases via oxidative post-translational modifications 94%
- Mass spectrometry of RNA-binding proteins during liquid-liquid phase separation reveals distinct assembly mechanisms and droplet architectures 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.