"Allosteric regulation of phosphorylation reader 14-3-3"

Allosteric regulation of the phosphorylation reader 14-3-3

Speaker: Diego M Bustos

Instituto de Histología y Embriología de Mendoza (IHEM) - Universidad Nacional de Cuyo - CONICET, Mendoza 5500, Argentina; F

Abstract:

14-3-3 proteins are a family of conserved regulatory proteins found only in eukaryotic organisms. These proteins are extraordinarily versatile and play critical roles in various cellular processes, including signal transduction, cell cycle control, and apoptosis (programmed cell death). They are involved in regulating numerous proteins and are known to interact with various targets, including enzymes, transcription factors, kinases, and receptors. As we initially discovered, 14-3-3 proteins function by binding to specific target proteins exclusively through interactions with an intrinsically disordered region containing a phosphorylatable serine/threonine residue. This binding can lead to a variety of outcomes, including changes in protein activity, localization, stability, or interaction with other molecules. By modulating the function of their binding partners, 14-3-3 proteins contribute to the regulation of various cellular processes and the maintenance of homeostasis. Originally thought to be non-regulated housekeeping proteins, we have discovered a novel allosteric site that induces a conformational change in 14-3-3 depending on its paralog. Our study reveals a dynamic conformation switch in which the affinity of 14-3-3 for its phosphorylation substrate changes dramatically in the presence or absence of a small molecule.