Signalling by co-operative higher-order assembly formation: linking evidence at molecular and cellular levels

Area of Science:

• Cellular Biology
• Biochemistry
• Molecular Signaling

Background:

• Signalling by co-operative assembly formation (SCAF) was proposed for protein assemblies using death-fold and Toll/interleukin-1 receptor domains.
• These domains form filamentous assemblies, activating pathways via induced proximity to sharpen response thresholds.

Purpose of the Study:

• To broaden the SCAF concept to include open-ended assembly kinetics in signaling.
• To compare filamentous and other co-operative assemblies, like biomolecular condensates.
• To review SCAF's operation within cellular contexts.

Main Methods:

• Conceptual expansion of SCAF.
• Comparative analysis of assembly types (filamentous vs. condensates).
• Literature review of SCAF in cellular pathways.

Main Results:

• SCAF mechanism features a nucleation barrier for switch-like, 'all-or-none' responses to stimuli.
• This binary signaling is essential in cell-death and innate immunity pathways.
• SCAF encompasses essential kinetic properties of open-ended assembly.

Conclusions:

• SCAF provides a framework for understanding digital cellular responses mediated by protein assemblies.
• The concept is applicable to diverse co-operative assembly mechanisms, including biomolecular condensates.
• SCAF is a fundamental signaling principle in critical cellular processes like immunity and cell death.