Structural basis of Focal Adhesion Kinase activation on lipid membranes.

ABSTRACT: Focal Adhesion Kinase (FAK) is a key component of the membrane-proximal signaling layer in focal adhesions, regulating important processes, including cell migration, proliferation and survival. In the cytosol, FAK adopts an autoinhibited state but is activated upon recruitment into focal adhesions, yet how this occurs or what induces structural changes is unknown. Here, we employ cryo-electron microscopy to reveal how FAK associates with lipid membranes and how membrane interactions unlock FAK autoinhibition to promote activation. Intriguingly, initial binding of FAK to the membrane causes steric clashes that release the kinase domain from autoinhibition, allowing it to rearrange and interact itself with the membrane in an orientation that places the active site towards the membrane. In t

SUBMITTER: Dr. Ivan Acebron 

PROVIDER: S-SCDT-EMBOJ-2020-104743 | biostudies-other |

REPOSITORIES: biostudies-other