Molecular basis for the evolved instability of a human G-protein coupled receptor

Laura Chamness, Nathan Zelt, Charles Kuntz, Brian Bender, Wesley Penn, Joshua Ziarek, Jens Meiler, Jonathan Schlebach & Haley Harrington
Membrane proteins are prone to misfolding and degradation. This is particularly true for mammalian forms of the gonadotropin-releasing hormone receptor (GnRHR). Although they function at the plasma membrane, mammalian GnRHRs accumulate within the secretory pathway. Their apparent instability is believed to have evolved through selection for attenuated GnRHR activity. Nevertheless, the molecular basis of this adaptation remains unclear. We show that adaptation coincides with a C-terminal truncation that compromises the translocon-mediated membrane integration of its...
2 citations reported since publication in 2020.
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