Evolving Notch polyQ tracts reveal possible solenoid interference elements

Area of Science:

• Evolutionary biology
• Structural biology
• Genetics

Background:

• Polyglutamine (polyQ) tracts are polymorphic and prone to mutations.
• Intrinsically disordered domains containing polyQ tracts are challenging to study.
• PolyQ expansions in Notch can cause developmental and neurogenic issues.

Purpose of the Study:

• Investigate structural principles of polyQ tracts in disordered regulatory domains.
• Analyze the evolution of metazoan Notch polyQ tracts.
• Identify conserved features and functional roles of polyQ insertion sites.

Main Methods:

• Deep evolutionary analysis of metazoan Notch polyQ tracts.
• Identification of conserved motifs and sequence features.
• Comparative analysis with other proteins like Huntingtin.

Main Results:

• Notch proteins exhibit polyQ tract turnover at specific conserved "polyQ insertion slots".
• These slots are characterized by a "slot leader" motif and are linked to ankyrin repeats (ARs).
• Slots are enriched in glutamine/asparagine residues, suggesting a role in interfering with AR folding.

Conclusions:

• Notch polyQ insertion slots function as "ankyrin repeat interference elements" (ARIEs).
• ARIEs dynamically compete with AR folding, modulating protein structure.
• Similar polyQ insertion sites in Huntingtin suggest a broader role for these elements in solenoid protein regulation.