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.
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http://purl.uniprot.org/cit... | rdf:type | uniprot:Journal_Citation | lld:uniprot |
http://purl.uniprot.org/cit... | rdfs:comment | 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. | lld:uniprot |
http://purl.uniprot.org/cit... | skos:exactMatch | http://purl.uniprot.org/pub... | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:name | J. Biol. Chem. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Pohl J. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Wang B. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Liddington R.C. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Petosa C. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Fu H. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Bankston L.A. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Masters S.C. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:date | 1998 | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:pages | 16305-16310 | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:title | 14-3-3zeta binds a phosphorylated Raf peptide and an unphosphorylated peptide via its conserved amphipathic groove. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:volume | 273 | lld:uniprot |
http://purl.uniprot.org/cit... | dc-term:identifier | doi:10.1074/jbc.273.26.16305 | lld:uniprot |
uniprot-protein:P63103 | uniprot:citation | http://purl.uniprot.org/cit... | lld:uniprot |
http://linkedlifedata.com/r... | uniprot:source | http://purl.uniprot.org/cit... | lld:uniprot |
http://linkedlifedata.com/r... | rdf:object | http://purl.uniprot.org/cit... | lld:uniprot |