Divergent Folding-Mediated Epistasis Among Unstable Membrane Protein Variants.

ABSTRACT: Many membrane proteins are prone to misfolding, which compromises their functional expression at the plasma membrane. This is particularly true for the mammalian gonadotropin-releasing hormone receptor GPCRs (GnRHR). We recently demonstrated that evolutionary GnRHR modifications appear to have coincided with adaptive changes in cotranslational folding efficiency. Though protein stability is known to shape evolution, it is unclear how cotranslational folding constraints modulate the synergistic, epistatic interactions between mutations. We therefore compared the pairwise interactions formed by mutations that disrupt the membrane topology (V276T) or tertiary structure (W107A) of GnRHR. Using deep mutational scanning, we evaluated how the plasma membrane expression of these variants is modifi

SUBMITTER: Chamness LM 

PROVIDER: S-EPMC10473758 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature