Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex

• Main Authors: Heddi, Brahim, Cheong, Vee Vee, Schmitt, Emmanuelle, Mechulam, Yves, Phan, Anh Tuân
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2021
• Subjects: Science::Biological sciences; G-quadruplex; X-ray Crystallography
• Online Access: https://hdl.handle.net/10356/150541
• Institution: Nanyang Technological University

G-quadruplexes (G4) are secondary structures of nucleic acids that can form in cells and have diverse biological functions. Several biologically important proteins interact with G-quadruplexes, of which RHAU (or DHX36) - a helicase from the DEAH-box superfamily, was shown to bind and unwind G-quadruplexes efficiently. We report a X-ray co-crystal structure at 1.5 Å resolution of an N-terminal fragment of RHAU bound to an exposed tetrad of a parallel-stranded G-quadruplex. The RHAU peptide folds into an L-shaped α-helix, and binds to a G-quadruplex through π-stacking and electrostatic interactions. X-ray crystal structure of our complex identified key amino acid residues important for G-quadruplex-peptide binding interaction at the 3'-end G•G•G•G tetrad. Together with previous solution and crystal structures of RHAU bound to the 5'-end G•G•G•G and G•G•A•T tetrads, our crystal structure highlights the occurrence of a robust G-quadruplex recognition motif within RHAU that can adapt to different accessible tetrads.