Asymmetric Modulation of Protein Order–Disorder Transitions by Phosphorylation and Partner Binding. (17th December 2015)

• Record Type: Journal Article
• Authors: Banerjee, Priya R.; Mitrea, Diana M.; Kriwacki, Richard W.; Deniz, Ashok A.
• Is Part Of: Angewandte Chemie. Volume 128:Number 5(2016)
• Page Start: 1707
• Page End: 1711
• Publication Date: 2015-12-17
• Subjects: Einzelmolekül-FRET -- Gekoppelte Faltung und Bindung -- Proteinfaltung -- Proteinkonformationen -- Reaktionskinetik; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201507728
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: As for many intrinsically disordered proteins, order–disorder transitions in the N‐terminal oligomerization domain of the multifunctional nucleolar protein nucleophosmin (Npm‐N) are central to its function, with phosphorylation and partner binding acting as regulatory switches. However, the mechanism of this transition and its regulation remain poorly understood. In this study, single‐molecule and ensemble experiments revealed pathways with alternative sequences of folding and assembly steps for Npm‐N. Pathways could be switched by altering the ionic strength. Phosphorylation resulted in pathway‐specific effects, and decoupled folding and assembly steps to facilitate disorder. Conversely, binding to a physiological partner locked Npm‐N in ordered pentamers and counteracted the effects of phosphorylation. The mechanistic plasticity found in the Npm‐N order–disorder transition enabled a complex interplay of phosphorylation and partner‐binding steps to modulate its folding landscape.