Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) RNA endoribonuclease nsp11 belongs to the XendoU superfamily and plays a crucial role in arterivirus replication. Here, we report the first crystal structure of the arterivirus nsp11 protein from PRRSV, which exhibits a unique structure and assembles into an asymmetric dimer whose structure is completely different from the hexameric structure of coronavirus nsp15. However, the structures of the PRRSV nsp11 and coronavirus nsp15 catalytic domains were perfectly superimposed, especially in the "active site loop" (His129 to His144) and "supporting loop" (Val162 to Thr179) regions. Importantly, our biochemical data demonstrated that PRRSV nsp11 exists mainly as a dimer in solution. Mutations of the major dimerization site determinants (Ser74 and Phe76) in the dimerization interface destabilized the dimer in solution and severely diminished endoribonuclease activity, indicating that the dimer is the biologically functional unit. In the dimeric structure, the active site loop and supporting loop are packed against one another and stabilized by monomer-monomer interactions. These findings may help elucidate the mechanism underlying arterivirus replication and may represent great potential for the development of antiviral drugs.
Original language | English (US) |
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Pages (from-to) | 4579-4592 |
Number of pages | 14 |
Journal | Journal of virology |
Volume | 90 |
Issue number | 9 |
DOIs | |
State | Published - May 1 2016 |
Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by the National Key Basic Research Plan (grant no. 2014CB542700), the National Natural Science Foundation of China (grant no. 31225027 and 31372440), and the Huazhong Agricultural University Scientific and Technological Self-innovation Foundation (program no. 2012RC008, 2013PY031, and 2662015JQ003).
Publisher Copyright:
© 2016, American Society for Microbiology. All Rights Reserved.