1A37

14-3-3 PROTEIN ZETA BOUND TO PS-RAF259 PEPTIDE

Summary for 1A37

• Entry DOI: 10.2210/pdb1a37/pdb
• Descriptor: 14-3-3 PROTEIN ZETA, PS-RAF259 PEPTIDE LSQRQRST(SEP)TPNVHM (2 entities in total)
• Functional Keywords: signal transduction, complex (signal transduction-peptide), complex (signal transduction-peptide) complex, complex (signal transduction/peptide)
• Biological source: Bos taurus (cattle)
• Cellular location: Cytoplasm: P63103
• Total number of polymer chains: 4
• Total formula weight: 59236.09

Authors

Petosa, C.,Masters, S.C.,Pohl, J.,Wang, B.,Fu, H.,Liddington, R.C. (deposition date: 1998-01-28, release date: 1999-03-02, Last modification date: 2024-10-23)

Primary citation

Petosa, C.,Masters, S.C.,Bankston, L.A.,Pohl, J.,Wang, B.,Fu, H.,Liddington, R.C.
14-3-3zeta binds a phosphorylated Raf peptide and an unphosphorylated peptide via its conserved amphipathic groove.
J.Biol.Chem., 273:16305-16310, 1998

PubMed Abstract: 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.

PubMed: 9632691
DOI: 10.1074/jbc.273.26.16305

Experimental method

X-RAY DIFFRACTION (3.6 Å)