- Evolutionary action and structural basis of the allosteric switch controlling β
Evolutionary action and structural basis of the allosteric switch controlling β
Nature communications (2017-12-20)
Anne-Marie Schönegge, Jonathan Gallion, Louis-Philippe Picard, Angela D Wilkins, Christian Le Gouill, Martin Audet, Wayne Stallaert, Martin J Lohse, Marek Kimmel, Olivier Lichtarge, Michel Bouvier
PMID29255305
要旨
Functional selectivity of G-protein-coupled receptors is believed to originate from ligand-specific conformations that activate only subsets of signaling effectors. In this study, to identify molecular motifs playing important roles in transducing ligand binding into distinct signaling responses, we combined in silico evolutionary lineage analysis and structure-guided site-directed mutagenesis with large-scale functional signaling characterization and non-negative matrix factorization clustering of signaling profiles. Clustering based on the signaling profiles of 28 variants of the β
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