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

D.M. BUSTOS, A.A. IGLESIAS

PROTEINS: STRUCTURE, FUNCTION AND GENETICS

Wiley-Liss, Inc.

Año: 2006 vol. 63 p. 35 - 42

0887-3585

ABSTRACT 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 differentcellular 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 all14-3-3-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.Proteins  2006;63:35?42.© 2006 Wiley-Liss, Inc.Key words: 14-3-3-binding site; protein?protein interaction;intrinsically disordered protein