Structural and functional characterization of the extended-diKH domain from the antiviral endoribonuclease KHNYN.

ABSTRACT: Zinc finger antiviral protein (ZAP) binds CpG dinucleotides in viral RNA and targets them for decay. ZAP interacts with several cofactors to form the ZAP antiviral system, including KHNYN, a multidomain endoribonuclease required for ZAP-mediated RNA decay. However, it is unclear how the individual domains in KHNYN contribute to its activity. Here, we demonstrate that the KHNYN amino-terminal extended-diKH (ex-diKH) domain is required for antiviral activity and present its crystal structure. The structure belongs to a rare group of KH-containing domains, characterized by a noncanonical arrangement between two type 1 KH modules, with an additional helical bundle. N4BP1 is a KHNYN paralog with an ex-diKH domain that functionally complements the KHNYN ex-diKH domain. Interestingly, the ex-diKH

SUBMITTER: Youle RL 

PROVIDER: S-EPMC11997328 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature