{PDOC51923}
{PS51923; COV_S2_HR1}
{PS51924; COV_S2_HR2}
{BEGIN}
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* Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) and 2 (HR2) regions profiles *
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Coronaviruses (CoVs)  [E1] are a diverse group of enveloped, plus-stranded RNA
viruses that  infect  humans  and many animal species, in which they can cause
respiratory, enteric,   hepatic,   central  nervous  system  and  neurological
diseases of  varying  severity.  A  CoV  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. This  protein  is  composed  of an N-terminal receptor-binding domain
(S1) and a C-terminal trans-membrane fusion domain (S2) [1,2,3].

The S2  subunit contains two 4-3 heptad repeats (HRs) of hydrophobic residues,
HR1 and HR2, typical of coiled coils, separated by an ~170-aa-long intervening
domain. The S2 subunit is expected to present rearrangement of its HRs to form
a stable 6-helix bundle fusion core [1,2,3].

HR1 forms  a  24-turn  alpha-helix, while HR2 adopts a mixed conformation: the
central part  fold  into a nine-turn alpha-helix, while the residues on either
side of  the helix adopt an extended conformation. The HR1 region forms a long
trimeric helical  coiled-coil  structure  with  peptides  from  the HR2 region
packing in  an oblique antiparallel manner on the grooves of the HR1 trimer in
a mixed  extended  and  helical  conformation (see <PDB:2BEZ>). Packing of the
helical parts  of HR2 on the HR1 trimer grooves and formation of a six-helical
bundle plays  an  important  role  in  the  formation  of a stable post-fusion
structure. In  contrast  to  their extended helical conformations in the post-
fusion state,  the  HR1 motifs within S2 form several shorter helices in their
pre-fusion state [1,2,3].

The profiles we developed cover the entire CoV S2-HR1 -HR2 regions.

-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: April 2020 / First entry.

[ 1] Supekar V.M., Bruckmann C., Ingallinella P., Bianchi E., Pessi A.,
     Carfi A.
     "Structure of a proteolytically resistant core from the severe acute
     respiratory syndrome coronavirus S2 fusion protein."
     Proc. Natl. Acad. Sci. U. S. A. 101:17958-17963(2004).
     PubMed=15604146; DOI=10.1073/pnas.0406128102
[ 2] Zhang W., Zheng Q., Yan M., Chen X., Yang H., Zhou W., Rao Z.
     "Structural characterization of the HCoV-229E fusion core."
     Biochem. Biophys. Res. Commun. 497:705-712(2018).
     PubMed=29458023; DOI=10.1016/j.bbrc.2018.02.136
[ 3] Yan L., Meng B., Xiang J., Wilson I.A., Yang B.
     "Crystal structure of the post-fusion core of the Human coronavirus
     229E spike protein at 1.86 A° resolution."
     Acta Crystallogr. D. Struct. Biol. 74:841-851(2018).
     PubMed=30198895; DOI=10.1107/S2059798318008318
[E1] https://viralzone.expasy.org/30?outline=all_by_species

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