Structure and Function of PRRSV nsp11 Endoribonuclease

Abstract

Endoribonuclease (NendoU) is conserved and plays essential roles in viral life cycle among all nidoviruses. Porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 11 (nsp11) is shown to have NendoU activity and its multifunctions have been demonstrated, such as processing RNA, suppressing innate immunity system of infected hosts and regulating the progression of S phase cells. We solve the crystal structure of PRRSV nsp11 mutant (K170A), and the overall structure is greatly different from severe acute respiratory syndrome coronaviruses (SARS-CoV) nsp15, the counterpart of nsp11 in coronaviruses. Compared with SARS-CoV nsp15 which has three domains, PRRSV nsp11 only have two domains: the N-terminal domain (NTD) and C-terminal domain (CTD). Smallangle X-ray scattering data shows that the PRRSV nsp11 has several kinds of oligomeric conformations in solution, this may be due to the missing domain, which mediates the hexamerization of SARS-CoV nsp15. The active center of NendoU is located in the CTD, where the conserved catalytic residues form a positively charged groove and bind the negatively charged RNA. The catalytic regions have several conformations, which are quite diverse. The NTD shares similar structural element with ubiquitin binding protein, but nsp11 cannot bind to ubiquitin according to our data. The flexible catalytic region of nidoviruses endoribonuclease confers an excellent target for drug design. These structural and functional information of PRRSV nsp11 would lay a foundation for better understanding of the molecular mechanism and antiviral drug development.