AI Article Synopsis
- The membrane around cells helps control how signals are sent by special receptors called G protein-coupled receptors, like the ghrelin receptor (GHSR).
- Certain fats called lipids can affect how well these receptors work, either by changing their shape or by sticking to them in a way that helps them activate.
- For example, one lipid, PIP2, helps the ghrelin receptor get activated more easily, while another lipid, GM3, also promotes activation but mostly when ghrelin is present; the thickness of the membrane also plays a role in this process.
Article Abstract
The membrane is an integral component of the G protein-coupled receptor signaling machinery. Here we demonstrate that lipids regulate the signaling efficacy and selectivity of the ghrelin receptor GHSR through specific interactions and bulk effects. We find that PIP2 shifts the conformational equilibrium of GHSR away from its inactive state, favoring basal and agonist-induced G protein activation. This occurs because of a preferential binding of PIP2 to specific intracellular sites in the receptor active state. Another lipid, GM3, also binds GHSR and favors G protein activation, but mostly in a ghrelin-dependent manner. Finally, we find that not only selective interactions but also the thickness of the bilayer reshapes the conformational repertoire of GHSR, with direct consequences on G protein selectivity. Taken together, this data illuminates the multifaceted role of the membrane components as allosteric modulators of how ghrelin signal could be propagated.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225672 | PMC |
| http://dx.doi.org/10.1038/s41467-021-23756-y | DOI Listing |
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