Protein G-quadruplex interactions and their effects on phase transitions and protein aggregation

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• The SERF protein family is known to accelerate amyloid formation.
• Znf706, an uncharacterized protein, shares N-terminal homology with SERF proteins.

Purpose of the Study:

• To investigate the function of human Znf706.
• To explore the interaction between Znf706 and G-quadruplexes.
• To understand the link between G-quadruplex binding and protein aggregation/gene regulation.

Main Methods:

• Protein aggregation assays.
• G-quadruplex binding studies (SPR).
• RNA sequencing (RNAseq) analysis.

Main Results:

• Human Znf706 promotes protein aggregation and amyloid formation.
• Znf706 specifically binds to parallel G-quadruplexes with low micromolar affinity.
• G-quadruplex binding constrains Znf706 dynamics and suppresses its aggregation-promoting activity.
• Znf706 depletion affects mRNA levels of genes with high G-quadruplex density.

Conclusions:

• Znf706 interacts with G-quadruplexes, modulating its own function and potentially regulating protein folding.
• The SERF protein family, via G-quadruplex interactions, may play a broader role in protein folding and gene expression regulation than previously understood.