PROSITE documentation PDOC51539
Arterivirus papain-like cysteine protease alpha and beta (PCPalpha and PCPbeta) domain profiles


Arteriviruses are enveloped, positive-stranded RNA viruses and include pathogens of major economic concern to the swine- and horse-breeding industries [E1]:

  - Equine arteritis virus (EAV).
  - Porcine reproductive and respiratory syndrome virus (PRRSV).
  - Mice actate dehydrogenase-elevating virus.
  - Simian hemorrhagic fever virus.

The arterivirus replicase gene is composed of two open reading frames (ORFs). ORF1a is translated directly from the genomic RNA, whereas ORF1b can be expressed only by ribosomal frameshifting, yelding a 1ab fusion protein. Both replicase gene products are multidomain precursor proteins which are proteolytically processed into functional nonstructural proteins (nsps) by a complex proteolytic cascade that is directed by four (PRRSV/LDV) or three (EAV) proteinase domains encoded in ORF1a. The arterivirus replicase processing scheme involves the rapid autoproteolytic release of two or three N-terminal nsps (nsp1 (or nsp1α/1β) and nsp2 (see <PDOC51538>)) and the subsequent processing of the remaining polyproteins by the "main protease" residing in nsp4 (see <PDOC51493>), together resulting in a set of 13 or 14 individual nsps. The arterivirus nsp1 region contains a tandem of papain-like cysteine autoprotease domains (PCPα and PCPβ), but in EAV PCPα has lost its enzymatic activity, resulting in the 'merge' of nsp1α and nsp1β into a single nsp1 subunit. Thus, instead of three self-cleaving N-terminal subunits, EAV has two: nsp1 and nsp2. The PCPα and PCPβ domains mediate the nsp1α|1β and nsp1β|2 cleavages, respectively. The catalytic dyad of PCPα and PCPβ domains is composed of Cys and His residues. In EAV, a Lys residue is found in place of the catalytic Cys residue, which explains the proteolytic deficiency of the EAV PCPα domain [1,2,3,4]. The PCPα and PCPβ domains form respectively peptidase families C31 [E2] and C32 [E3].

The PCPα and PCPβ domains have a typical papain fold, which consists of a compact global region containing sequentially connected left (L) and right (R) parts in a so-called standard orientation. The L subdomain of PCPα consists of four α-helices, while the R subdomain is formed by three antiparallel β strands (see <PDB:3IFU>) [5]. The L subdomain of the PCBβ consists of three α-helices, while the R subdomain is formed by four antiparallel β-strands (see <PDB:3MTV>) [6]. The Cys and His residues face each other at the L-R interface and form the catalytic center of the PCPα and PCPβ domains [5,6].

The profiles we developed cover the entire PCPα and PCPβ domains.

Last update:

May 2011 / First entry.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

AV_PCP_ALPHA, PS51539; Arterivirus papain-like cysteine protease alpha (PCPalpha) domain profile  (MATRIX)

AV_PCP_BETA, PS51540; Arterivirus papain-like cysteine protease beta (PCPbeta) domain profile  (MATRIX)


1Authorsden Boon J.A. Faaberg K.S. Meulenberg J.J.M. Wassenaar A.L.M. Plagemann P.G.W. Gorbalenya A.E. Snijder E.J.
TitleProcessing and evolution of the N-terminal region of the arterivirus replicase ORF1a protein: identification of two papainlike cysteine proteases.
SourceJ. Virol. 69:4500-4505(1995).
PubMed ID7769711

2AuthorsZiebuhr J. Snijder E.J. Gorbalenya A.E.
TitleVirus-encoded proteinases and proteolytic processing in the Nidovirales.
SourceJ. Gen. Virol. 81:853-879(2000).
PubMed ID10725411

3AuthorsTijms M.A. van Dinten L.C. Gorbalenya A.E. Snijder E.J.
TitleA zinc finger-containing papain-like protease couples subgenomic mRNA synthesis to genome translation in a positive-stranded RNA virus.
SourceProc. Natl. Acad. Sci. U.S.A. 98:1889-1894(2001).
PubMed ID11172046

4AuthorsFang Y. Snijder E.J.
TitleThe PRRSV replicase: exploring the multifunctionality of an intriguing set of nonstructural proteins.
SourceVirus Res. 154:61-76(2010).
PubMed ID20696193

5AuthorsSun Y. Xue F. Guo Y. Ma M. Hao N. Zhang X.C. Lou Z. Li X. Rao Z.
TitleCrystal structure of porcine reproductive and respiratory syndrome virus leader protease Nsp1alpha.
SourceJ. Virol. 83:10931-10940(2009).
PubMed ID19706710

6AuthorsXue F. Sun Y. Yan L. Zhao C. Chen J. Bartlam M. Li X. Lou Z. Rao Z.
TitleThe crystal structure of porcine reproductive and respiratory syndrome virus nonstructural protein Nsp1beta reveals a novel metal-dependent nuclease.
SourceJ. Virol. 84:6461-6471(2010).
PubMed ID20410261




PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)