title: Structural insights of the MLF1/14-3-3 interaction.
abstract: Myeloid leukaemia factor 1 (MLF1) binds to 14-3-3 adapter proteins by a sequence surrounding Ser34 with the functional consequences of this interaction largely unknown. We present here the high-resolution crystal structure of this binding motif [MLF1(29-42)pSer34] in complex with 14-3-3ε and analyse the interaction with isothermal titration calorimetry. Fragment-based ligand discovery employing crystals of the binary 14-3-3ε/MLF1(29-42)pSer34 complex was used to identify a molecule that binds to the interface rim of the two proteins, potentially representing the starting point for the development of a small molecule that stabilizes the MLF1/14-3-3 protein-protein interaction. Such a compound might be used as a chemical biology tool to further analyse the 14-3-3/MLF1 interaction without the use of genetic methods. Database Structural data are available in the Protein Data Bank under the accession number(s) 3UAL [14-3-3ε/MLF1(29-42)pSer34 complex] and 3UBW [14-3-3ε/MLF1(29-42)pSer34/3-pyrrolidinol complex] Structured digital abstract •  14-3-3 epsilon and MLF1 bind by x-ray crystallography (View interaction) •  14-3-3 epsilon and MLF1 bind by isothermal titration calorimetry (View Interaction: 1, 2).
authors.affiliation: Chemical Genomics Centre of the Max-Planck-Society, Dortmund, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Molzan
authors.forename: Michael
authors.initials: M
authors.lastname: Weyand
authors.forename: Rolf
authors.initials: R
authors.lastname: Rose
authors.forename: Christian
authors.initials: C
authors.lastname: Ottmann
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002151:Calorimetry / Q000379:methods; D018797:Cell Cycle Proteins; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012694:Serine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C100852:MLF1 protein, human; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; D012694:Serine