Solution‐State Structure of a Long‐Loop G‐Quadruplex Formed Within Promoters of Plasmodium falciparum B var Genes

We report the high‐resolution NMR solution‐state structure of an intramolecular G‐quadruplex with a diagonal loop of ten nucleotides. The G‐quadruplex is formed by a 34‐nt DNA sequence, d[CAG3T2A2G3TATA2CT3AG4T2AG3T2], named UpsB‐Q‐1. This sequence is found within promoters of the var genes of Plasm...

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Bibliographic Details
Published in:Chemistry : a European journal 2024-06, Vol.30 (36), p.e202401190-n/a
Main Authors: Juribašić Kulcsár, Marina, Gabelica, Valérie, Plavec, Janez
Format: Article
Language:English
Subjects:
Base stacking
G-quadruplex
Genes
Guanines
Hybrid systems
Hydrogen bonding
Immune system
long loop
loop interactions
Malaria
NMR
Nuclear magnetic resonance
Nucleotide sequence
Nucleotides
Pathogenesis
Plasmodium falciparum
Promoters
Residues
Vector-borne diseases
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Summary:We report the high‐resolution NMR solution‐state structure of an intramolecular G‐quadruplex with a diagonal loop of ten nucleotides. The G‐quadruplex is formed by a 34‐nt DNA sequence, d[CAG3T2A2G3TATA2CT3AG4T2AG3T2], named UpsB‐Q‐1. This sequence is found within promoters of the var genes of Plasmodium falciparum, which play a key role in malaria pathogenesis and evasion of the immune system. The [3+1]‐hybrid G‐quadruplex formed under physiologically relevant conditions exhibits a unique equilibrium between two structures, both stabilized by base stacking and non‐canonical hydrogen bonding. Unique equilibrium of the two closely related 3D structures originates from a North‐South repuckering of deoxyribose moiety of residue T27 in the lateral loop. Besides the 12 guanines involved in three G‐quartets, most residues in loop regions are involved in interactions at both G‐quartet‐loop interfaces. We report a high‐resolution NMR solution‐state structure of an intramolecular [3+1]‐hybrid G‐quadruplex formed by a 34‐nt DNA sequence, d[CAG3T2A2G3TATA2CT3AG4T2AG3T2]. The G‐quadruplex with a diagonal 10‐nt loop shows a unique equilibrium between two structures, both stabilized by base stacking and non‐standard hydrogen bonding. In addition to the 12 guanines involved in three G‐quartets, most residues in the loop regions are well defined and involved in the interactions.
ISSN:0947-6539
1521-3765
1521-3765
DOI:10.1002/chem.202401190