Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors.

ABSTRACT: Mammalian odorant receptors are a diverse and rapidly evolving set of G protein-coupled receptors expressed in olfactory cilia membranes. Most odorant receptors show little to no cell surface expression in nonolfactory cells due to endoplasmic reticulum retention, which has slowed down biochemical studies. Here we provide evidence that structural instability and divergence from conserved residues of individual odorant receptors underlie intracellular retention using a combination of large-scale screening of odorant receptors cell surface expression in heterologous cells, point mutations, structural modeling, and machine learning techniques. We demonstrate the importance of conserved residues by synthesizing consensus odorant receptors that show high levels of cell surface expression simila

SUBMITTER: Ikegami K 

PROVIDER: S-EPMC7022149 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature