1a37
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14-3-3 PROTEIN ZETA BOUND TO PS-RAF259 PEPTIDE
OverviewOverview
14-3-3 proteins bind a variety of molecules involved in signal, transduction, cell cycle regulation and apoptosis. 14-3-3 binds ligands, such as Raf-1 kinase and Bad by recognizing the phosphorylated consensus, motif, RSXpSXP, but must bind unphosphorylated ligands, such as, glycoprotein Ib and Pseudomonas aeruginosa exoenzyme S, via a different, motif. Here we report the crystal structures of the zeta isoform of 14-3-3, in complex with two peptide ligands: a Raf-derived phosphopeptide, (pS-Raf-259, LSQRQRSTpSTPNVHMV) and an unphosphorylated peptide derived, from phage display (R18, PHCVPRDLSWLDLEANMCLP) that inhibits binding of, exoenzyme S and Raf-1. The two peptides bind within a conserved, amphipathic groove on the surface of 14-3-3 at overlapping but distinct, sites. The phosphoserine of pS-Raf-259 engages a cluster of basic residues, (Lys49, Arg56, Arg60, and Arg127), whereas R18 binds via the amphipathic, sequence, WLDLE, with its two acidic groups coordinating the same basic, cluster. 14-3-3 is dimeric, and its two peptide-binding grooves are, arranged in an antiparallel fashion, 30 A apart. The ability of each, groove to bind different peptide motifs suggests how 14-3-3 can act in, signal transduction by inducing either homodimer or heterodimer formation, in its target proteins.
About this StructureAbout this Structure
1A37 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
14-3-3zeta binds a phosphorylated Raf peptide and an unphosphorylated peptide via its conserved amphipathic groove., Petosa C, Masters SC, Bankston LA, Pohl J, Wang B, Fu H, Liddington RC, J Biol Chem. 1998 Jun 26;273(26):16305-10. PMID:9632691
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