Structure of the Sec14 domain of Kalirin reveals a distinct class of lipid-binding module in RhoGEFs.

ABSTRACT: Gated entry of lipophilic ligands into the enclosed hydrophobic pocket in stand-alone Sec14 domain proteins often links lipid metabolism to membrane trafficking. Similar domains occur in multidomain mammalian proteins that activate small GTPases and regulate actin dynamics. The neuronal RhoGEF Kalirin, a central regulator of cytoskeletal dynamics, contains a Sec14 domain (Kal^bSec14) followed by multiple spectrin-like repeats and catalytic domains. Previous studies demonstrated that Kalirin lacking its Sec14 domain fails to maintain cell morphology or dendritic spine length, yet whether and how Kal^bSec14 interacts with lipids remain unknown. Here, we report the structural and biochemical characterization of Kal^bSec14. Kal^bSec14 adopts a closed con

SUBMITTER: Li Y 

PROVIDER: S-EPMC9823006 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature