Abstract:
:The approximately 30-kb coronavirus (+)RNA genome is replicated and transcribed by a membrane-bound replicase complex made up of 16 viral nonstructural proteins (nsp) with multiple enzymatic activities. The complex includes an RNA endonuclease, NendoU, that is conserved among nidoviruses but no other RNA virus, making it a genetic marker of this virus order. NendoU (nsp15) is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond. Neither biochemical nor sequence homology criteria allow a classification of nsp15 into existing endonuclease families. Here, we report the crystal structure of the severe acute respiratory syndrome coronavirus nsp15 at 2.6-A resolution. Nsp15 exhibits a unique fold and assembles into a toric hexamer with six potentially active, peripheric catalytic sites. The structure and the spatial arrangement of the catalytic residues into an RNase A-like active site define a separate endonuclease family, endoU, and represent another spectacular example of convergent evolution toward an enzymatic function that is critically involved in the coronavirus replication cycle.
journal_name
Proc Natl Acad Sci U S Aauthors
Ricagno S,Egloff MP,Ulferts R,Coutard B,Nurizzo D,Campanacci V,Cambillau C,Ziebuhr J,Canard Bdoi
10.1073/pnas.0601708103subject
Has Abstractpub_date
2006-08-08 00:00:00pages
11892-7issue
32eissn
0027-8424issn
1091-6490pii
0601708103journal_volume
103pub_type
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