Membrane-mimetic thermal proteome profiling (MM-TPP) toward mapping membrane protein-ligand dynamic interactions.

ABSTRACT: Integral membrane proteins (IMPs) are central targets for small-molecule therapeutics, yet robust, unbiased, and detergent-free approaches to assess their on- and off-target interactions remain limited. Previously, we introduced the Peptidisc membrane mimetic (MM) for water-soluble stabilization of the membrane proteome and interactome (Carlson et al., eLife, 2019). In this work, we combine the Peptidisc with thermal proteome profiling (TPP) to establish membrane-mimetic thermal proteome profiling (MM-TPP), a method that enables proteome-wide mapping of membrane protein-ligand interactions. Using a membrane protein library derived from mouse liver tissue, we detected the specific effects of ATP and orthovanadate on the thermal stability of ATP-binding cassette (ABC) transporters, as well a

SUBMITTER: Jandu RS 

PROVIDER: S-EPMC12611261 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature