Bulged and Canonical G-Quadruplex Conformations Determine NDPK Binding Specificity

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Guanine-rich DNA sequences can form G-quadruplex (G4) structures.
• G4s are stabilized by cations and involve Hoogsteen base-paired guanine stacks.
• Conformational heterogeneity in G4s is increasingly recognized for its biological significance.

Purpose of the Study:

• To investigate the conformational heterogeneity of a G-rich sequence from the 5' untranslated region of the Zea mays hexokinase4 gene.
• To determine how adjacent guanine incorporation affects G4 polymorphism.
• To examine the interaction of the maize nucleoside diphosphate kinase 1 (ZmNDPK1) protein with these G4 conformations.

Main Methods:

• Analysis of G-rich DNA sequences from Zea mays hexokinase4.
• Investigation of G-quadruplex formation and conformational polymorphism in solution.
• Biochemical assays to assess protein-G4 interactions.

Main Results:

• The studied G-rich sequence exhibits extensive G-quadruplex conformational polymorphism.
• Non-canonical bulged G-quadruplex folds co-exist in solution.
• Polymorphism is influenced by the incorporation of different guanine sets into the quadruplex core.
• ZmNDPK1 specifically recognizes and promotes a subset of these G4 conformations.

Conclusions:

• G-rich sequences can display significant G-quadruplex conformational heterogeneity.
• The interplay between DNA sequence and protein binding dictates specific G4 structure formation.
• Understanding G4 polymorphism is crucial for exploring their roles in gene regulation and host-pathogen interactions, with potential implications for microbial G4s.