Abstract：
:Numerous drugs and endogenous ligands bind to cell surface receptors leading to modulation of downstream signaling cascades and frequently to adaptation of the plasma membrane proteome. In-depth analysis of dynamic processes at the cell surface is challenging due to biochemical properties and low abundances of plasma membrane proteins. Here we introduce cell surface thermal proteome profiling for the comprehensive characterization of ligand-induced changes in protein abundances and thermal stabilities at the plasma membrane. We demonstrate drug binding to extracellular receptors and transporters, discover stimulation-dependent remodeling of T cell receptor complexes and describe a competition-based approach to measure target engagement of G-protein-coupled receptor antagonists. Remodeling of the plasma membrane proteome in response to treatment with the TGFB receptor inhibitor SB431542 leads to partial internalization of the monocarboxylate transporters MCT1/3 explaining the antimetastatic effects of the drug.
journal_name
Nat Methodsjournal_title
Nature methodsauthors
Kalxdorf M,Günthner I,Becher I,Kurzawa N,Knecht S,Savitski MM,Eberl HC,Bantscheff Mdoi
10.1038/s41592-020-01022-1subject
Has Abstractpub_date
2021-01-01 00:00:00pages
84-91issue
1eissn
1548-7091issn
1548-7105pii
10.1038/s41592-020-01022-1journal_volume
18pub_type
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