ANCHOR RESIDUES IN 14-3-3 AND PHOSPHOPROTEIN COMPLEXES DETERMINED BY MOLECULAR DYNAMICS

DIEGO M BUSTOS, ALBERTO A IGLESIAS

Pinamar

Congreso; Sociedad Argentina de Investigacion Bioquimica y Biologia Molecular; 2005

SAIB

Proteins named 14-3-3 can bind more than 200 different proteins, mostly at a phosphorylated state. These partner proteins are involved in different cellular processes, as cell signaling, transcription factors, cellular morphology and metabolism; which 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. We propose that a disorder-to-order transition occurs in the binding of 14-3-3 proteins with their partners. This induced fit process contributes to form the final high-affinity complex. To avoid a kinetically costly search for correct structure, it is necessary that specific amino acid side chain (structurally constrained) helps to stabilize a native-like bound intermediate. We identify the anchor residues in a protein-protein complex of 14-3-3 by using molecular dynamics protocols in explicit solvent box and verify that, even in the absence of their interacting partners, the anchor side chain is found in conformations similar to those observed in the bound complex. Kinetic and thermodynamics implications for the binding between 14-3-3 and its partners are discussed.