The ≈30-kb coronavirus (+)RMA 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 Mn2+-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-Å 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.
Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family / S. Ricagno, M. Egloff, R. Ulferts, B. Coutard, D. Nurizzo, V. Campanacci, C. Cambillau, J. Ziebuhr, B. Canard. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 103:32(2006 Aug 08), pp. 11892-11897.
|Titolo:||Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family|
RICAGNO, STEFANO (Primo)
|Parole Chiave:||endonuclease; nidovirus; replication; severe acute respiratory syndrome; amino acid sequence; binding sites; catalytic domain; crystallography, x-ray; endonucleases; endoribonucleases; models, molecular; molecular sequence data; protein conformation; protein structure, tertiary; rna replicase; sars virus; sequence homology, amino acid; viral nonstructural proteins; virus replication; multidisciplinary|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||8-ago-2006|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1073/pnas.0601708103|
|Appare nelle tipologie:||01 - Articolo su periodico|