nsp9

Nsp9 is generated when SARS 3CLpro cleaves at the nsp8/9 and nsp9/10 boundaries of the replicase polyprotein PP1a/1ab.  It is known to colocalize in the perinuclear region along with other components of the replication complex . Two groups have independently determined the structure of nsp9. It adopts a beta-barrel fold with a C-terminal alpha-helix. nsp9 is structurally homologous to subdomains of serine proteases, in particular the second domain of the coronavirus 3CL^pro. Sequence analysis reveals that the N and C termini of the protein are more conserved than the central core region. Nsp9 binds ssRNA and dsDNA in a concentration dependent manner. Optimal binding occurs with 45-mer oligonucleotides, consistent with binding occurring by the nsp9 dimer wrapping the DNA fragment around itself once. Since RNA-binding is not sequence specific, nsp9 may protect nascent ssRNA from nucleases during viral RNA synthesis, given its natural abundance in the infected cell.

Bost, A. G., Carnahan, R. H., Lu, X. T., and Denison, M. R.  2000.  Four proteins processed from the replicase gene polyprotein of mouse hepatitis virus colocalize in the cell periphery and adjacent to sites of virion assembly.  J. Virol. 74: 3379-87.

Ponnusamy R, Mesters JR, Ziebuhr J, Moll R, Hilgenfeld R. Non structural proteins 8 and 9 of human coronavirus 229E. Adv Exp Med Biol. 2006;581:49-54.

Egloff MP, Ferron F, Campanacci V, Longhi S, Rancurel C, Dutartre H, Snijder EJ, Gorbalenya AE, Cambillau C, Canard B. The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world. Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3792-6. Epub 2004 Mar 8.

Prentice E, McAuliffe J, Lu X, Subbarao K, Denison MR. Identification and characterization of severe acute respiratory syndrome coronavirus replicase proteins.J Virol. 2004 Sep;78(18):9977-86.

Sutton G, Fry E, Carter L, Sainsbury S, Walter T, Nettleship J, Berrow N, Owens R, Gilbert R, Davidson A, Siddell S, Poon LL, Diprose J, Alderton D, Walsh M, Grimes JM, Stuart DI.  The nsp9 replicase protein of SARS-coronavirus, structure and functional insights. Structure (Camb). 2004 Feb;12(2):341-53.

Campanacci V, Egloff MP, Longhi S, Ferron F, Rancurel C, Salomoni A, Durousseau C, Tocque F, Bremond N, Dobbe JC, Snijder EJ, Canard B, Cambillau C. Structural genomics of the SARS coronavirus: cloning, expression, crystallization and preliminary crystallographic study of the Nsp9 protein. Acta Crystallogr D Biol Crystallogr. 2003 Sep;59(Pt 9):1628-31.

Bartlam M, Yang H, Rao Z. Structural insights into SARS coronavirus proteins. Curr Opin Struct Biol. 2005 Dec;15(6):664-72.