Hindered intermolecular stacking of anti-parallel telomeric G-quadruplexes

Area of Science:

• Biochemistry
• Structural Biology
• Nanotechnology

Background:

• Telomeric G-quadruplexes (G4s) are crucial for genome stability.
• G4s are explored as building blocks in synthetic biology and nanotechnology.
• Understanding G4 topology is key to predicting their interactions.

Purpose of the Study:

• Investigate the end-to-end stacking of antiparallel telomeric G-quadruplexes.
• Determine how G4 topology affects multimerization.
• Analyze the influence of diagonal loops on G4 stacking.

Main Methods:

• Small-angle X-ray scattering (SAXS) was employed.
• A coarse-grained fitting tool was developed for data analysis.
• Experimental data were fitted to models of monomeric and dimeric G4 species.

Main Results:

• Antiparallel G4s exist as an equilibrium mixture of monomers and dimers.
• Long multimeric structures were not observed under self-crowding conditions.
• Diagonal loops significantly influence the stacking of monomeric G-quadruplexes.

Conclusions:

• Antiparallel G4 topology restricts the formation of extensive multimers.
• G4 structure and topology dictate their self-assembly behavior.
• Findings provide insights into G4 interactions relevant to genome stability and synthetic applications.