Open AccessA membrane protein display platform for receptor interactome discovery
Author(s) -
Shengya Cao,
Sean M. Peterson,
Sören Müller,
Mike Reichelt,
Christian McRoberts Amador,
Nadia MartínezMartín
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2025451118
Subject(s) - interactome , transmembrane protein , drug discovery , membrane protein , microbiology and biotechnology , protein–protein interaction , signal transduction , computational biology , biology , g protein coupled receptor , receptor , chemistry , membrane , bioinformatics , biochemistry , gene
Significance Membrane proteins and their interactions are major drug targets because of their central roles in regulating cellular communication and signal transduction. Despite this, membrane receptors remain underrepresented in our knowledge base of protein–protein interactions because of the limitations of most available techniques. Here, we developed a vesicle-based membrane-protein display platform as a fast, reproducible, and broadly applicable method for unbiased receptor–ligand interaction discovery. Using this technology, we elucidated known and new single-pass transmembrane-binding partners for several immune checkpoint molecules as well as an architecturally distinct single-pass transmembrane protein that has resisted deorphanization by existing techniques. This method is well suited for extracellular protein interaction discovery for difficult-to-purify membrane proteins and whole vesicles.