title: Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex.
abstract: Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex-protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures.
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371.
authors.forename: Brahim
authors.initials: B
authors.lastname: Heddi
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371.
authors.forename: Vee Vee
authors.initials: VV
authors.lastname: Cheong
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371.
authors.forename: Herry
authors.initials: H
authors.lastname: Martadinata
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 phantuan@ntu.edu.sg.
authors.forename: Anh Tuân
authors.initials: AT
authors.lastname: Phan
mesh_terms: D000595:Amino Acid Sequence; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D054856:G-Quadruplexes; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: D050505:Mutant Proteins; D010455:Peptides; D012996:Solutions; D053487:DEAD-box RNA Helicases
keywords: DEAH-box family; DHX36; G-quadruplex; NMR; RHAU helicase