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Publication Abstract from PubMed

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 ZC3H12A C proteins. The RNA is bound in the central groove region of the protein, facilitated by interactions including coordination by two Mg(2+) ions, hydrophobic interactions, and hydrogen bonds. In the observed RNA-protein complex, the U(5), A(6), and U(7) bases are stacked on top of one another, while U(3) and U(4) 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.

Crystal structure of NYN domain of Human KHNYN in complex with single strand RNA.,Hong S, Choe J Biochem Biophys Res Commun. 2024 Aug 13;738:150545. doi: , 10.1016/j.bbrc.2024.150545. PMID:39167961^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.