{PDOC51539}
{PS51539; AV_PCP_ALPHA}
{PS51540; AV_PCP_BETA}
{BEGIN}
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* Arterivirus papain-like cysteine protease alpha and beta (PCPalpha and PCPbeta) domain profiles *
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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 nsp1alpha/1beta) 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 (PCPalpha and PCPbeta), but in EAV
PCPalpha has  lost  its  enzymatic  activity,  resulting  in  the  'merge'  of
nsp1alpha and  nsp1beta  into  a  single  nsp1 subunit. Thus, instead of three
self-cleaving N-terminal  subunits,  EAV  has two: nsp1 and nsp2. The PCPalpha
and PCPbeta  domains  mediate  the  nsp1alpha|1beta  and nsp1beta|2 cleavages,
respectively. The  catalytic  dyad of PCPalpha and PCPbeta 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
PCPalpha domain  [1,2,3,4]. The PCPalpha and PCPbeta domains form respectively
peptidase families C31 [E2] and C32 [E3].

The PCPalpha and PCPbeta 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 PCPalpha
consists of  four  alpha-helices,  while  the  R  subdomain is formed by three
antiparallel beta strands (see <PDB:3IFU>) [5]. The L subdomain of the PCBbeta
consists of  three  alpha-helices,  while  the  R  subdomain is formed by four
antiparallel beta-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 PCPalpha
and PCPbeta domains [5,6].

The profiles we developed cover the entire PCPalpha and PCPbeta domains.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: May 2011 / First entry.

[ 1] den Boon J.A., Faaberg K.S., Meulenberg J.J.M., Wassenaar A.L.M.,
     Plagemann P.G.W., Gorbalenya A.E., Snijder E.J.
     "Processing and evolution of the N-terminal region of the arterivirus
     replicase ORF1a protein: identification of two papainlike cysteine
     proteases."
     J. Virol. 69:4500-4505(1995).
     PubMed=7769711
[ 2] Ziebuhr J., Snijder E.J., Gorbalenya A.E.
     "Virus-encoded proteinases and proteolytic processing in the
     Nidovirales."
     J. Gen. Virol. 81:853-879(2000).
     PubMed=10725411
[ 3] Tijms M.A., van Dinten L.C., Gorbalenya A.E., Snijder E.J.
     "A zinc finger-containing papain-like protease couples subgenomic mRNA
     synthesis to genome translation in a positive-stranded RNA virus."
     Proc. Natl. Acad. Sci. U.S.A. 98:1889-1894(2001).
     PubMed=11172046; DOI=10.1073/pnas.041390398
[ 4] Fang Y., Snijder E.J.
     "The PRRSV replicase: exploring the multifunctionality of an
     intriguing set of nonstructural proteins."
     Virus Res. 154:61-76(2010).
     PubMed=20696193; DOI=10.1016/j.virusres.2010.07.030
[ 5] Sun Y., Xue F., Guo Y., Ma M., Hao N., Zhang X.C., Lou Z., Li X.,
     Rao Z.
     "Crystal structure of porcine reproductive and respiratory syndrome
     virus leader protease Nsp1alpha."
     J. Virol. 83:10931-10940(2009).
     PubMed=19706710; DOI=10.1128/JVI.02579-08
[ 6] Xue F., Sun Y., Yan L., Zhao C., Chen J., Bartlam M., Li X., Lou Z.,
     Rao Z.
     "The crystal structure of porcine reproductive and respiratory
     syndrome virus nonstructural protein Nsp1beta reveals a novel
     metal-dependent nuclease."
     J. Virol. 84:6461-6471(2010).
     PubMed=20410261; DOI=10.1128/JVI.00301-10
[E1] https://viralzone.expasy.org/284?outline=all_by_species
[E2] https://www.ebi.ac.uk/merops/cgi-bin/famsum?family=c31
[E3] https://www.ebi.ac.uk/merops/cgi-bin/famsum?family=c32

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