Probing ion channel functional architecture and domain recombination compatibility by massively parallel domain insertion profiling.

ABSTRACT: Protein domains are the basic units of protein structure and function. Comparative analysis of genomes and proteomes showed that domain recombination is a main driver of multidomain protein functional diversification and some of the constraining genomic mechanisms are known. Much less is known about biophysical mechanisms that determine whether protein domains can be combined into viable protein folds. Here, we use massively parallel insertional mutagenesis to determine compatibility of over 300,000 domain recombination variants of the Inward Rectifier K⁺ channel Kir2.1 with channel surface expression. Our data suggest that genomic and biophysical mechanisms acted in concert to favor gain of large, structured domain at protein termini during ion channel evolution. We use machine

SUBMITTER: Coyote-Maestas W 

PROVIDER: S-EPMC8654947 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature