title: Cyclophilin A binds to linear peptide motifs containing a consensus that is present in many human proteins.
abstract: Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans-isomerase that is involved in multiple signaling events of eukaryotic cells. It might either act as a catalyst for prolyl bond isomerization, or it can form stoichiometric complexes with target proteins. We have investigated the linear sequence recognition code for CypA by phage display and found the consensus motif FGPXLp to be selected after five rounds of panning. The peptide FGPDLPAGD showed inhibition of the isomerase reaction and NMR chemical shift mapping experiments highlight the CypA interaction epitope. Ligand docking suggests that the peptide was able to bind to CypA in the cis- and trans-conformation. Protein Data Bank searches reveal that many human proteins contain the consensus motif, and several of these protein motifs are shown to interact with CypA in vitro. These sequences represent putative target sites for binding of CypA to intracellular proteins.
authors.affiliation: Protein Engineering Group, Freie Universität Berlin and Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Kirill
authors.initials: K
authors.lastname: Piotukh
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.forename: Michael
authors.initials: M
authors.lastname: Kofler
authors.forename: Dirk
authors.initials: D
authors.lastname: Labudde
authors.forename: Volkhard
authors.initials: V
authors.lastname: Helms
authors.forename: Christian
authors.initials: C
authors.lastname: Freund
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001435:Bacteriophages / Q000235:genetics; D021984:Cyclophilin A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D010455:Peptides; D011994:Recombinant Proteins; D021984:Cyclophilin A