{PDOC51922}
{PS51922; BCOV_S1_NTD}
{BEGIN}
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* Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile *
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Coronaviruses (CoVs)  [E1] primarily cause respiratory and enteric diseases in
humans, animals,  and  birds,  and  some  CoVs  also  cause systemic diseases,
including hepatitis  or  neurological  diseases.  Phylogenetically,  CoVs  are
divided into four genera, called the alpha-, beta-, gamma-, and delta-CoVs. Of
these, betacoronaviruses  (betaCoVs)  [E1]  have attracted attention worldwide
because of  their pathogenic capacity and potential to cause a global pandemic
of human  infections  and  the  widespread  existence of an enormous number of
species in  bats. Three highly pathogenic human coronaviruses (CoVs) have been
identified so  far,  including  Middle  East  respiratory syndrome coronavirus
(MERS-CoV), severe  acute  respiratory syndrome (SARS) coronavirus (SARS-CoV),
and a 2019 novel coronavirus SARS-CoV-2 [1,2,3,4].

A coronavirus contains four structural proteins, including spike (S), envelope
(E), membrane  (M),  and nucleocapsid (N) proteins. Among them, the S protein,
which is  located on the  envelope surface of the virion, functions to mediate
receptor recognition  and  membrane  fusion  and  is  therefore  a  key factor
determining the   virus  tropism  for  a  specific  species.  In  most  cases,
coronaviral S  will  be  further  cleaved  into  S1  and  S2 subunits, and the
receptor binding capacity is allocated to the S1 subunit. The receptor binding
domain (RBD) of betaCoV that directly engages the receptor is commonly located
in the  C-terminal  half  of S1 [C-terminal domain (CTD)] such as in SARS-CoV,
SARS-CoV-2, MERS-CoV,and  BatCoV HKU4, though in rare cases such as with mouse
hepatitis virus  (MHV),  the  RBD  region  was identified in the S1 N-terminal
domain (NTD), which mainly recognizes sugar receptors [1,2,3,4].

The betaCoV  NTDs  contain a conserved beta-sandwich core, but exhibit variant
folds in  the peripheral elements located in the top-ceiling region and on the
lateral side  (see  <PDB:6JHY>).  The core sandwich comprises in total sixteen
anti-parallel beta-strands,  assembling  into three (upper, middle, and lower)
beta-sheet layers.  While  showing  different compositions and structures, the
peripheral elements    are    topologically    equivalent   beta-sandwich-core
insertions, highlighting  a  divergent  evolution process for betaCoVs to form
different lineages [2].

The profile we developed covers the entire betaCoV S1-NTD 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] Qian Z., Ou X., Goes L.G., Osborne C., Castano A., Holmes K.V.,
     Dominguez S.R.
     "Identification of the Receptor-Binding Domain of the Spike
     Glycoprotein of Human  Betacoronavirus HKU1."
     J. Virol. 89:8816-8827(2015).
     PubMed=26085157; DOI=10.1128/JVI.03737-14
[ 2] Cheng Y., He B., Yang J., Ye F., Lin S., Yang F., Chen Z., Chen Z.,
     Cao Y., Lu G.
     "Crystal structure of the S1 subunit N-terminal domain from DcCoV
     UAE-HKU23 spike  protein."
     Virology 535:74-82(2019).
     PubMed=31279241; DOI=10.1016/j.virol.2019.06.015
[ 3] Shang J., Wan Y., Liu C., Yount B., Gully K., Yang Y., Auerbach A.,
     Peng G., Baric R., Li F.
     "Structure of mouse coronavirus spike protein complexed with receptor
     reveals mechanism for viral entry."
     PLoS Pathog. 16:E1008392-E1008392(2020).
     PubMed=32150576; DOI=10.1371/journal.ppat.1008392
[ 4] Wang N., Rosen O., Wang L., Turner H.L., Stevens L.J., Corbett K.S.,
     Bowman C.A., Pallesen J., Shi W., Zhang Y., Leung K.,
     Kirchdoerfer R.N., Becker M.M., Denison M.R., Chappell J.D.,
     Ward A.B., Graham B.S., McLellan J.S.
     "Structural Definition of a Neutralization-Sensitive Epitope on the
     MERS-CoV S1-NTD."
     Cell. Rep. 28:3395-3405.e6(2019).
     PubMed=31553909; DOI=10.1016/j.celrep.2019.08.052
[E1] https://viralzone.expasy.org/764?outline=all_by_species

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