Dataset: Distinct functional constraints driving conservation of the cofilin N-terminal regulatory tail

External ID

GSE242403

Channels

1

Conditions

14

Description

Cofilin family proteins have essential roles in remodeling the cytoskeleton through filamentous actin depolymerization and severing. The short unstructured N-terminal region of cofilin is critical for actin binding and harbors the major site of inhibitory phosphorylation. Atypically for a disordered sequence, the N-terminal region is highly conserved, but specifics aspects driving this conservation are unclear. Here, we screened a library of 16,000 human cofilin N-terminal sequence variants for their capacity to support growth in S. cerevisiae in the presence or absence of the upstream regulator LIM kinase. Results from the screen and biochemical analysis of individual variants revealed distinct sequence requirements for actin binding and regulation by LIM kinase. LIM kinase recognition only partly explained sequence constraints on phosphoregulation, which were instead driven to a large extent by the capacity for phosphorylation to inactivate cofilin. We found remarkably loose sequence requirements for actin binding and phosphoinhibition, but collectively they restricted the N-terminus to sequences found in natural cofilins. Our results illustrate how a phosphorylation site can balance potentially competing sequence requirements for function and regulation.

Categories

cytoskeleton and molecular motors

GEO