{PDOC51919}
{PS51919; X4E}
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* Sarbecovirus X4e domain profile *
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Coronaviruses are  enveloped  positive-strand  RNA  viruses  that  infect many
species, including humans, other mammals, and birds. After infection, the host
may develop    respiratory,   bowel,   liver,   and   neurological   diseases.
Coronaviruses are divided into four genera: Alphacoronavirus, Betacoronavirus,
Gammacoronavirus, and  Deltacoronavirus.  SARS,  SARS-CoV-2, BatCoV RaTG13 and
Bat-SARS-like coronavirus  (BATSL-CoVZXC21  and  BAT-SL-CoVZC45) belong to the
Sarbecovirus subgenus of Betacoronavirus [1,2,3,E1].

Coronaviruses code  for  the  characteristic  proteins  replicase  polyprotein
(pp1ab), spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins.
In addition, Sarbecoviruses code for subgroup-specific accessory proteins that
are thought  to  be dispensable for viral replication in cell culture, but may
be important  for  virus-host  interactions  and thus contribute to the virus'
fitness [1].

The Sarbecovirus accessory protein X4, also called 7a or U122, is likely to be
a type I membrane protein, with the amino-terminal hydrophilic domain oriented
inside the  lumen  of  the  ER/Golgi or on the surface of the cell membrane or
virus particle,  depending  on  the  localization  of the protein. It has been
suggested that  X4e  contains a binding site for the alpha(L) integrin subunit
I-domain of LFA-1 [1,2].

The X4   ectodomain  (X4e)  forms  a  well  defined  beta-sandwich  fold  (see
<PDB:1YO4>). It  is built up from seven beta-strands so that four strands form
one beta-sheet  and  three strands form a second sheet. The sheets are closely
packed or  'sandwiched' against each other. Each sheet is amphipathic with the
hydrophobic side  facing  inward. The larger four-stranded beta-sheet consists
of strands  A,  G, F, and C, the smaller three-stranded beta-sheet consists of
strands B,  E,  and  D.  The  overall  appearance  of the seven stranded beta-
sandwich fold  of  the  X4e  domain very much reminds one to an immunoglobulin
(Ig) like  fold, that shows some features resembling those of the Dl domain of
ICAM-1. All  beta-strands  align in anti-parallel fashion, as it is well-known
for most  immunoglobulin-like  domains,  with the exception of strand A, which
aligns parallel  to strand G. Two disulfide bonds link both sheets on opposite
edges therefore  stabilizing  the beta-sandwich structure. The first disulfide
of X4e  connects  the  end  of  strand  A  to  the  E-F loop, while the second
disulfide connects the short B-C and F-G loops [1,2].

The profile we developed covers the entire X4e domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: March 2020 / First entry.

[ 1] Haenel K., Stangler T., Stoldt M., Willbold D.
     "Solution structure of the X4 protein coded by the SARS related
     coronavirus reveals an immunoglobulin like fold and suggests a binding
     activity to integrin I domains."
     J. Biomed. Sci. 13:281-293(2006).
     PubMed=16328780; DOI=10.1007/s11373-005-9043-9
[ 2] Nelson C.A., Pekosz A., Lee C.A., Diamond M.S., Fremont D.H.
     "Structure and intracellular targeting of the SARS-coronavirus Orf7a
     accessory protein."
     Structure 13:75-85(2005).
     PubMed=15642263; DOI=10.1016/j.str.2004.10.010
[ 3] Fahmi M., Kubota Y., Ito M.
     "Nonstructural proteins NS7b and NS8 are likely to be phylogenetically
     associated  with evolution of 2019-nCoV."
     Infect. Genet. Evol. 81:104272-104272(2020).
     PubMed=32142938; DOI=10.1016/j.meegid.2020.104272
[E1] https://viralzone.expasy.org/30?outline=all_by_species

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