2N21

Solution structure of complex between DNA G-quadruplex and G-quadruplex recognition domain of RHAU

Summary for 2N21

• Entry DOI: 10.2210/pdb2n21/pdb
• NMR Information: BMRB: 25582
• Descriptor: ATP-dependent RNA helicase DHX36, DNA (5'-D(*TP*TP*GP*GP*GP*TP*GP*GP*GP*TP*GP*GP*GP*TP*GP*GP*GP*T)-3') (2 entities in total)
• Functional Keywords: hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q9H2U1
• Total number of polymer chains: 2
• Total formula weight: 8091.47

Authors

Heddi, B.,Cheong, V.V.,Martadinata, H.,Phan, A.T. (deposition date: 2015-04-25, release date: 2015-07-29, Last modification date: 2024-05-15)

Primary citation

Heddi, B.,Cheong, V.V.,Martadinata, H.,Phan, A.T.
Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex.
Proc.Natl.Acad.Sci.USA, 112:9608-9613, 2015

PubMed 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.

PubMed: 26195789
DOI: 10.1073/pnas.1422605112

Experimental method

SOLUTION NMR