Spatial covariance analysis reveals the residue-by-residue thermodynamic contribution of variation to the CFTR fold.

ABSTRACT: Although the impact of genome variation on the thermodynamic properties of function on the protein fold has been studied in vitro, it remains a challenge to assign these relationships across the entire polypeptide sequence in vivo. Using the Gaussian process regression based principle of Spatial CoVariance, we globally assign on a residue-by-residue basis the biological thermodynamic properties that contribute to the functional fold of CFTR in the cell. We demonstrate the existence of a thermodynamically sensitive region of the CFTR fold involving the interface between NBD1 and ICL4 that contributes to its export from endoplasmic reticulum. At the cell surface a new set of residues contribute uniquely to the management of channel function. These results support a general 'quality assurance

SUBMITTER: Angles F 

PROVIDER: S-EPMC9008016 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature