Intrinsic disorder is a key characteristic in partners that bind 14-3-3 proteins

• Autores: Bustos, Diego Martin; Iglesias, Alberto Alvaro
• Año de publicación: 2006
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: 14-3-3-BINDING SITE; INTRINSICALLY DISORDERED PROTEIN; PROTEIN-PROTEIN INTERACTION
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Bustos, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Iglesias, Alberto Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Enzimología Molecular; Argentina