Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling

• Published in: Structure (London) Vol. 26; no. 2; pp. 259 - 269.e5
• Main Authors: White, Kate L., Eddy, Matthew T., Gao, Zhan-Guo, Han, Gye Won, Lian, Tiffany, Deary, Alexander, Patel, Nilkanth, Jacobson, Kenneth A., Katritch, Vsevolod, Stevens, Raymond C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 06.02.2018; Elsevier
• Subjects: adenosine receptor; allosteric modulators; Allosteric Regulation - physiology; Allosteric Site - physiology; cell signaling; crystallography; GPCR; Humans; Protein Binding; Protein Conformation; Receptors, G-Protein-Coupled - metabolism; Signal Transduction - physiology; sodium binding; structural biology; crystallography; cell signaling; allosteric modulators; sodium binding; adenosine receptor; GPCR; structural biology

Sodium ions are endogenous allosteric modulators of many G-protein-coupled receptors (GPCRs). Mutation of key residues in the sodium binding motif causes a striking effect on G-protein signaling. We report the crystal structures of agonist complexes for two variants in the first sodium coordination...