Structural basis for distinct quality control mechanisms of GABA(B)receptor during evolution

[摘要] Cell surface trafficking of many G protein-coupled receptors is tightly regulated. Among them, the mandatory heterodimer GABA(B)receptor for the main inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), is a model. In mammals, its cell surface trafficking is highly controlled by an endoplasmic reticulum retention signal in the C-terminal intracellular region of the GB1 subunit that is masked through a coiled-coil interaction with the GB2 subunit. Here, we investigate the molecular basis for the export of its homolog inDrosophila melanogasterthat regulates the circadian rhythm and sleep. In contrast to mammals, the endoplasmic retention signal is carried by GB2, while GB1 reaches the cell surface alone. NMR analysis showed that the coiled-coil domain that controls GABA(B)heterodimer formation is structurally conserved between flies and mammals, despite specific features. These findings show the adaptation of a similar quality control system during evolution for maintaining the subunit composition of a functional heterodimeric receptor.

[发布日期] 2020-12-01

[关键词] ENDOPLASMIC-RETICULUM RETENTION;GABA(B) RECEPTOR;NMR-SPECTROSCOPY;SURFACE TRAFFICKING;GB2 SUBUNITS;EXPRESSION;DOMAIN;HETERODIMERIZATION;GABA(B)-RECEPTOR;CRYSTALLOGRAPHY