Details

Autor(en) / Beteiligte

• Guan, Jian
• Jakob, Ursula

Titel

The Protein Scaffolding Functions of Polyphosphate

Ist Teil von

• Journal of molecular biology, 2024-07, Vol.436 (14), p.168504, Article 168504

Ort / Verlag

Netherlands: Elsevier Ltd

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• [Display omitted] •Polyphosphate is an ancestral and universally abundant polyanion.•Polyphosphate acts as mul5func5onal protein scaffold.•Polyphosphate solubilizes protein unfolding intermediates.•Polyphosphate modulates func5onal and disease-associated amyloid forma5on.•Polyphosphate promotes phase separa5on of na5ve proteins. Inorganic polyphosphate (polyP), one of the first high-energy compound on earth, defies its extreme compositional and structural simplicity with an astoundingly wide array of biological activities across all domains of life. However, the underlying mechanism of such functional pleiotropy remains largely elusive. In this review, we will summarize recent studies demonstrating that this simple polyanion stabilizes protein folding intermediates and scaffolds select native proteins. These functions allow polyP to act as molecular chaperone that protects cells against protein aggregation, as pro-amyloidogenic factor that accelerates both physiological and disease-associated amyloid formation, and as a modulator of liquid–liquid phase separation processes. These activities help to explain polyP’s known roles in bacterial stress responses and pathogenicity, provide the mechanistic foundation for its potential role in human neurodegenerative diseases, and open a new direction regarding its influence on gene expression through condensate formation. We will highlight critical unanswered questions and point out potential directions that will help to further understand the pleiotropic functions of this ancient and ubiquitous biopolymer.