Entangled World of DNA Quadruplex Folds

DNA quadruplexes participate in many biological functions.
It takes
up a variety of folds based on the sequence and environment. Here,
a meticulous analysis of experimentally determined 437 quadruplex
structures (433 PDBs) deposited in the PDB is carried out. The analysis
reveals the modular representation of the quadruplex folds. Forty-eight
unique quadruplex motifs (whose diversity arises out of the propeller,
bulge, diagonal, and lateral loops that connect the quartets) are
identified, leading to simple to complex inter/intramolecular quadruplex
folds. The two-layered structural motifs are further classified into
33 continuous and 15 discontinuous motifs. While the continuous motifs
can directly be extended to a quadruplex fold, the discontinuous motif
requires an additional loop(s) to complete a fold, as illustrated
here with examples. Similarly, higher-order quadruplex folds can also
be represented by continuous or discontinuous motifs or their combinations.
Such a modular representation of the quadruplex folds may assist in
custom engineering of quadruplexes, designing motif-based drugs, and
the prediction of the quadruplex structure. Furthermore, it could
facilitate understanding of the role of quadruplexes in biological
functions and diseases.