title: Structure of N-terminal domain of ZAP indicates how a zinc-finger protein recognizes complex RNA.
abstract: Zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses, such as HIV-1, by targeting viral mRNA for degradation. How ZAP recognizes its target RNA has been unclear. Here we report the crystal structure of the N-terminal domain of rat ZAP (NZAP225), the major functional domain. The overall structure of NZAP225 resembles a tractor, with four zinc-finger motifs located at the bottom. Structural and functional analyses identified multiple positively charged residues and two putative RNA-binding cavities forming a large putative RNA-binding cleft. ZAP molecules interact to form a dimer that binds to a ZAP-responsive RNA molecule containing two ZAP-binding modules. These results provide insights into how ZAP binds specifically to complex target RNA.
authors.affiliation: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Shoudeng
authors.initials: S
authors.lastname: Chen
authors.forename: Yihui
authors.initials: Y
authors.lastname: Xu
authors.forename: Kuo
authors.initials: K
authors.lastname: Zhang
authors.forename: Xinlu
authors.initials: X
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Guangxia
authors.initials: G
authors.lastname: Gao
authors.forename: Yingfang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins; D051381:Rats; D016415:Sequence Alignment; D016335:Zinc Fingers
chemical_list: D002352:Carrier Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C465959:Zc3hav1 protein, rat