Structure of the complex of phosphorylated liver kinase B1 and 14-3-3ζ

The serine/threonine protein kinase liver kinase B1 (LKB1) is a tumour suppressor and plays important roles in development and metabolism. It phosphorylates AMPK and AMPK-related kinases to regulate multiple physiological processes. Mutations in LKB1 often occur in multiple cancers. LKB1 can be suppressed by 14-3-3 proteins in a phosphorylation-dependent manner. Previously, the structure of a 14-3-3ζ-LKB1 fusion protein has been reported, revealing a phosphorylation-independent binding mode of LKB1 to 14-3-3 proteins. Here, the crystal structure of phosphorylated LKB1 peptide in complex with 14-3-3ζ was solved, which provides a structural basis for the phosphorylation-dependent recognition of LKB1 by 14-3-3 proteins.