{PDOC51960}
{PS51960; COV_NSP15_NTD}
{BEGIN}
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* Coronavirus (CoV) Nsp15 N-terminal oligomerization domain profile *
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Coronaviruses (CoVs)  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.  The  ideal  hosts  of  AlphaCoV  and
BetaCoV are  mammals, and GammaCoV primarily infects birds, while DeltaCoV has
been identified in both mammals and birds. SARS, SARS-CoV-2, BatCoV RaTG13 and
Bat-SARS-like coronavirus  (BATSL-CoVZXC21  and  BAT-SL-CoVZC45) belong to the
Sarbecovirus subgenus of BetaCoV [E1].

The CoV  replicase  gene encodes two overlapping polyproteins, termed pp1a and
pp1ab, which  mediate  viral  replication  and transcription. The polypeptides
pp1a and  pp1ab  are  processed  by  the action of a main protease (Nsp5) (see
<PDOC51442>) and of one or two papain-like proteases (PLpro) (see <PDOC51124>)
found in  Nsp3  into  non-structural  proteins (Nsps) to form the replication/
transcription complex  (RTC).  Among  them,  Nsp15  is  a nidoviral uridylate-
specific endoribonuclease  (NendoU)  that  plays an essential role in the life
cycle of  the  virus. CoV Nsp15 consists of three distinct domains, a small N-
terminal, an  intermediate-sized  middle, and a large C-terminal NendoU domain
(see <PDOC51958>).  CoV  Nsp15  forms  double-ring  hexamers made of dimers of
trimers. The  hexameric  form  is  thought  to be the fully active form of CoV
Nsp15 and  the  hexamer  is  stabilized  by  interactions  of  the  N-terminal
oligomerization domain [1,2,3,4,5,6,7].

The CoV  Nsp15 NTD oligomerization domain is composed of an antiparallel beta-
sheet (strands  beta1,  beta2,  and  beta3)  wrapped  around two alpha-helices
(alpha1 and alpha2) (see <PDB:6VWW>) [5,6,7].

The profile   we   developed   covers   the   entire   CoV   Nsp15  N-terminal
oligomerization domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: February 2021 / First entry.

[ 1] Snijder E.J., Decroly E., Ziebuhr J.
     "The Nonstructural Proteins Directing Coronavirus RNA Synthesis and
     Processing."
     Adv. Virus. Res. 96:59-126(2016).
     PubMed=27712628; DOI=10.1016/bs.aivir.2016.08.008
[ 2] Gorgulla C., Das K.M.P., Leigh K.E., Cespugli M., Fischer P.D.,
     Wang Z.-F., Tesseyre G., Pandita S., Shnapir A., Calderaio A.,
     Hutcheson C., Gechev M., Rose A., Lewis N., Yaffe E., Luxenburg R.,
     Herce H.D., Durmaz V., Halazonetis T.D., Fackeldey K., Patten J.J.,
     Chuprina A., Dziuba I., Plekhova A., Moroz Y., Radchenko D.,
     Tarkhanova O., Yavnyuk I., Gruber C.C., Yust R., Payne D., Naeaer A.M.,
     Namchuk M.N., Davey R.A., Wagner G., Kinney J., Arthanari H.
     "A Multi-Pronged Approach Targeting SARS-CoV-2 Proteins Using
     Ultra-Large Virtual  Screening."
     ChemRxiv 0:0-0(2020).
     PubMed=33200116; DOI=10.26434/chemrxiv.12682316
[ 3] Xu X., Zhai Y., Sun F., Lou Z., Su D., Xu Y., Zhang R., Joachimiak A.,
     Zhang X.C., Bartlam M., Rao Z.
     "New antiviral target revealed by the hexameric structure of mouse
     hepatitis virus nonstructural protein nsp15."
     J. Virol. 80:7909-7917(2006).
     PubMed=16873248; DOI=10.1128/JVI.00525-06
[ 4] Zheng A., Shi Y., Shen Z., Wang G., Shi J., Xiong Q., Fang L.,
     Xiao S., Fu Z.F., Peng G.
     "Insight into the evolution of nidovirus endoribonuclease based on the
     finding that nsp15 from porcine Deltacoronavirus functions as a
     dimer."
     J. Biol. Chem. 293:12054-12067(2018).
     PubMed=29887523; DOI=10.1074/jbc.RA118.003756
[ 5] Joseph J.S., Saikatendu K.S., Subramanian V., Neuman B.W.,
     Buchmeier M.J., Stevens R.C., Kuhn P.
     "Crystal structure of a monomeric form of severe acute respiratory
     syndrome coronavirus endonuclease nsp15 suggests a role for
     hexamerization as an allosteric switch."
     J. Virol. 81:6700-6708(2007).
     PubMed=17409150; DOI=10.1128/JVI.02817-06
[ 6] Zhang L., Li L., Yan L., Ming Z., Jia Z., Lou Z., Rao Z.
     "Structural and Biochemical Characterization of Endoribonuclease Nsp15
     Encoded by  Middle East Respiratory Syndrome Coronavirus."
     J. Virol. 92:0-0(2018).
     PubMed=30135128; DOI=10.1128/JVI.00893-18
[ 7] Kim Y., Jedrzejczak R., Maltseva N.I., Wilamowski M., Endres M.,
     Godzik A., Michalska K., Joachimiak A.
     "Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2."
     Protein. Sci. 29:1596-1605(2020).
     PubMed=32304108; DOI=10.1002/pro.3873
[E1] https://viralzone.expasy.org/30?outline=all_by_species

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