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Structural insights of the MLF1/14‐3‐3 interaction
Author(s) -
Molzan Manuela,
Weyand Michael,
Rose Rolf,
Ottmann Christian
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08445.x
Subject(s) - isothermal titration calorimetry , chemistry , computational biology , protein–protein interaction , biology , crystallography , biochemistry
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 )