Structural basis of 14-3-3 protein functions

Regulation of the Subcellular Localization of the G-protein Subunit Regulator GPSM3 through Direct Association with 14-3-3 Protein

“…S2A). 14-3-3 binding sites are often localized within disordered regions of a protein; it is thought that interaction with disordered regions facilitates ligand capture and transition from a disordered to ordered state that stabilizes complex formation (25,26).…”

“…Consensus recognition motifs for 14-3-3 binding targets, although not absolute, are R(S/)(ϩ)pSXP (mode I) and RX(/S)(ϩ)(pS)XP (mode II) where pS is phosphoserine, ϩ is a basic amino acid, is an aromatic residue, and X is any type of residue (25,27 S2). The last two sites do not match perfectly with the consen- sus motifs, but numerous 14-3-3 binding partners contain sequences that differ significantly from these optimal motifs (27).…”

“…The 14-3-3 dimer adopts a cup-like shape that can interact simultaneously with two binding sites within the same protein, thereby inducing conformational change and regulating protein activity or regulating other interactions via competition or occlusion. The presence of only one 14-3-3 binding site in GPSM3 and the binding of either dimeric or monomeric 14-3-3 to GPSM3 suggest that the 14-3-3 interaction could represent an important scaffolding function and/or stabilize formation of a multiprotein complex (21,25).…”

Structure of the 14-3-3ζ–LKB1 fusion protein provides insight into a novel ligand-binding mode of 14-3-3

“…Seven 14-3-3 isoforms have been identified in mammals, named 14-3-3 , 14-3-3", 14-3-3 , 14-3-3 , 14-3-3 , 14-3-3 and 14-3-3 (Ichimura et al, 1988;Martin et al, 1993). All 14-3-3 proteins show a high similarity in sequence and structure, forming a clamp-shaped dimer with each subunit consisting of a highly conserved ligand-binding groove created by nine antiparallel -helices (Obsil & Obsilova, 2011). 14-3-3 proteins were the first class of proteins that were discovered to be specific phosphoserine (pS)/phosphothreonine (pT) binding proteins. The target proteins usually share one of two common binding motifs: RSXpS/pTXP (mode I) or RXXXpS/pTXP (mode II) (where X represents any residue; Obsil & Obsilova, 2011;Rittinger et al, 1999;Yaffe et al, 1997).…”

“…All 14-3-3 proteins show a high similarity in sequence and structure, forming a clamp-shaped dimer with each subunit consisting of a highly conserved ligand-binding groove created by nine antiparallel -helices (Obsil & Obsilova, 2011). 14-3-3 proteins were the first class of proteins that were discovered to be specific phosphoserine (pS)/phosphothreonine (pT) binding proteins. The target proteins usually share one of two common binding motifs: RSXpS/pTXP (mode I) or RXXXpS/pTXP (mode II) (where X represents any residue; Obsil & Obsilova, 2011;Rittinger et al, 1999;Yaffe et al, 1997). In these two binding modes, the phosphorylated residue pS/pT of the target protein is recognized by a positively charged pocket within the ligand-binding groove of the 14-3-3 protein.…”