Molecular switches in GPCRs. (April 2019)

• Record Type: Journal Article
• Authors: Filipek, Slawomir
• Is Part Of: Current opinion in structural biology. Volume 55(2019)
• Page Start: 114
• Page End: 120
• Publication Date: 2019-04
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2019.03.017
• Languages: English
• ISSNs: 0959-440X

Abstract

Graphical abstract: Highlights: GPCRs are key players in cell-cell communication and pass the signal via coordinated action of switches. There are two types of switches: toggle switches and locks. The action of switches can be permanent or temporary. Receptor activation is associated with breaking of hydrophobic barriers and influx of water molecules. Abstract : Molecular switches in GPCRs enable passing the signal from the agonist binding site, usually located close to the extracellular surface, to the intracellular part of the receptor. The switches are usually associated with conserved structural motifs on transmembrane helices (TMs), and they are accompanied by adjacent residues which provide the signal to the central residue in the toggle switch. In case of locks being the molecular switches, they are breaking (permanently or temporarily) upon agonist binding. Cascade action of switches is correlated with influx of water molecules to form a pathway linking both sides of the receptor. The switches remove the hydrophobic barriers and facilitate water movement while water molecules help to rearrange the hydrogen bond network inside the receptor.