Intrinsic disorder is a key characteristic in partners that bind 14-3-3 proteins.
Proteins named 14-3-3 can bind more than 200 different proteins, mostly (but not exclusively) when they are at a phosphorylated state. These partner proteins are involved in different cellular processes, such as cell signaling, transcription factors, cellular morphology, and metabolism; this suggests pleiotropic functionality for 14-3-3 proteins. Recent efforts to establish a rational classification of 14-3-3 binding partners showed neither structural nor functional relatedness in this group of proteins. Using three natural predictors of disorder in proteins, and the structural available information, we show that >90% of 14-3-3 protein partners contain disordered regions. This percentage is significantly high when compared with recent studies on cell signaling and cancer-related proteins or RNA chaperons. More important, almost all 14-3-3-binding sites are inside disordered regions, this reinforcing the importance of structural disorder in this class of proteins. We also propose that a disorder-to-order transition occurs in the binding of 14-3-3 proteins with their partners. We discuss the consequences of the latter for consensus binding sequences, specificity, affinity, and thermodynamic control.
Bustos
Diego M
DM
Instituto Tecnológico de Chascomús-IIB-INTECH, Camino Circunvalación, Chascomús, Argentina. dbustos@intech.gov.ar
Iglesias
Alberto A
AA
D048948:14-3-3 Proteins / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans; D019295:Computational Biology / Q000379:methods*; D004331:Drosophila melanogaster; D006801:Humans; D008958:Models, Molecular; D008962:Models, Theoretical; D008968:Molecular Conformation; D010766:Phosphorylation; D011120:Polyomavirus / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D040901:Proteomics / Q000379:methods*; D012313:RNA / Q000737:chemistry; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D048948:14-3-3 Proteins; D012313:RNA