Determinants of trafficking, conduction, and disease within a K⁺ channel revealed through multiparametric deep mutational scanning.

ABSTRACT: A long-standing goal in protein science and clinical genetics is to develop quantitative models of sequence, structure, and function relationships to understand how mutations cause disease. Deep mutational scanning (DMS) is a promising strategy to map how amino acids contribute to protein structure and function and to advance clinical variant interpretation. Here, we introduce 7429 single-residue missense mutations into the inward rectifier K⁺ channel Kir2.1 and determine how this affects folding, assembly, and trafficking, as well as regulation by allosteric ligands and ion conduction. Our data provide high-resolution information on a cotranslationally folded biogenic unit, trafficking and quality control signals, and segregated roles of different structural elements in fold st

SUBMITTER: Coyote-Maestas W 

PROVIDER: S-EPMC9273215 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature