Systematic profiling of temperature- and retinal-sensitive rhodopsin variants by deep mutational scanning.

ABSTRACT: Membrane protein variants with diminished conformational stability often exhibit enhanced cellular expression at reduced growth temperatures. The expression of "temperature-sensitive" variants is also typically sensitive to corrector molecules that bind and stabilize the native conformation. There are many examples of temperature-sensitive rhodopsin variants, the misfolding of which is associated with the molecular basis of retinitis pigmentosa. In this work, we employ deep mutational scanning to compare the effects of reduced growth temperature and 9-cis-retinal, an investigational corrector, on the plasma membrane expression of 700 rhodopsin variants in HEK293T cells. We find that the change in expression at reduced growth temperatures correlates with the response to 9-cis-retinal among

SUBMITTER: McKee AG 

PROVIDER: S-EPMC8649220 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature