SNAP output for PDB entry 8wzc [SNAP web server]

PDB-id

8wzc; SNAP-derived features in text and JSON formats; DNAproDB

Class

hydrolase-RNA

Method

X-ray (1.925 Å)

Summary

Nyn domain of human khnyn complex with RNA

Reference

Hong S, Choe J (2024): "Crystal structure of NYN domain of Human KHNYN in complex with single strand RNA." Biochem.Biophys.Res.Commun., 738, 150545. doi: 10.1016/j.bbrc.2024.150545.

Abstract

KHNYN protein with a KH-like domain and a NYN endoribonuclease domain interacts with Zinc-finger antiviral protein (ZAP). ZAP isoforms recognize viral or cellular RNAs and recruit KHNYN to form the ZAP: KHNYN complex. Although the structures of several PIN/NYN domains have been determined, the precise substrate RNA binding mode remains poorly understood. This study presents the crystal structure of a complex of the NYN domain of KHNYN and a 7mer RNA from interferon lambda3 (IFNL3). Our structural analysis reveals that NYN domain of human KHNYN shares structural similarities with other NYN domains of ZC3H12àC proteins. The RNA is bound in the central groove region of the protein, facilitated by interactions including coordination by two Mg₂₊ ions, hydrophobic interactions, and hydrogen bonds. In the observed RNA-protein complex, the U₅, A₆, and U₇ bases are stacked on top of one another, while U₃ and U₄ bases adopt an "open" conformation (as opposed to base-stacked), forming a U-shaped overall structure. Mutagenesis studies underscore the significance of residues involved in RNA binding for RNase activity. Interestingly, NYN domain of human KHNYN forms a head-to-tail dimer in the crystal, a structural feature also observed in other homologous PIN/NYN proteins, with a residue from the symmetry mate contributing to hydrophobic interactions with the bound RNA.