1A37: 14-3-3 Protein Zeta Bound To Ps-raf259 Peptide

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.
PDB ID: 1A37Download
MMDB ID: 142537
PDB Deposition Date: 1998/1/28
Updated in MMDB: 2016/08
Experimental Method:
x-ray diffraction
Resolution: 3.6  Å
Source Organism:
Bos taurus
Similar Structures:
Biological Unit for 1A37: tetrameric; determined by author
Molecular Components in 1A37
Label Count Molecule
Proteins (4 molecules)
14-3-3 Protein Zeta(Gene symbol: YWHAZ)
Molecule annotation
Ps-raf259 Peptide Lsqrqrst(sep)tpnvhm
Molecule annotation
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Citing MMDB