Domain insertion permissibility-guided engineering of allostery in ion channels.

ABSTRACT: Allostery is a fundamental principle of protein regulation that remains hard to engineer, particularly in membrane proteins such as ion channels. Here we use human Inward Rectifier K⁺ Channel Kir2.1 to map site-specific permissibility to the insertion of domains with different biophysical properties. We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility. Several regions in Kir2.1 that are equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K⁺ channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain. Our data and the well-established link between protein dynamics and allostery led us to p

SUBMITTER: Coyote-Maestas W 

PROVIDER: S-EPMC6336875 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature