Abstract
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.
Keywords:
14-3-3 proteins; Peutz–Jeghers syndrome; complexes; crystal structure; liver kinase B1; phosphorylation; tumour suppression.
MeSH terms
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14-3-3 Proteins / chemistry*
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14-3-3 Proteins / genetics
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14-3-3 Proteins / metabolism
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AMP-Activated Protein Kinase Kinases
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Amino Acid Motifs
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Binding Sites
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Cloning, Molecular
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Crystallography, X-Ray
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Genetic Vectors / chemistry
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Genetic Vectors / metabolism
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Humans
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Liver / chemistry*
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Liver / enzymology
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Models, Molecular
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Phosphorylation
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Protein Binding
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Protein Conformation, alpha-Helical
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Protein Interaction Domains and Motifs
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
Substances
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14-3-3 Proteins
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Recombinant Proteins
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YWHAZ protein, human
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Protein Serine-Threonine Kinases
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STK11 protein, human
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AMP-Activated Protein Kinase Kinases