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PROSITE documentation PDOC51923
Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) and 2 (HR2) regions profiles


Description

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 α-helix, while HR2 adopts a mixed conformation: the central part fold into a nine-turn α-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.

Last update:

April 2020 / First entry.

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Technical section

PROSITE methods (with tools and information) covered by this documentation:

COV_S2_HR1, PS51923; Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile  (MATRIX)

COV_S2_HR2, PS51924; Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile  (MATRIX)


References

1AuthorsSupekar V.M. Bruckmann C. Ingallinella P. Bianchi E. Pessi A. Carfi A.
TitleStructure of a proteolytically resistant core from the severe acute respiratory syndrome coronavirus S2 fusion protein.
SourceProc. Natl. Acad. Sci. U. S. A. 101:17958-17963(2004).
PubMed ID15604146
DOI10.1073/pnas.0406128102

2AuthorsZhang W. Zheng Q. Yan M. Chen X. Yang H. Zhou W. Rao Z.
TitleStructural characterization of the HCoV-229E fusion core.
SourceBiochem. Biophys. Res. Commun. 497:705-712(2018).
PubMed ID29458023
DOI10.1016/j.bbrc.2018.02.136

3AuthorsYan L. Meng B. Xiang J. Wilson I.A. Yang B.
TitleCrystal structure of the post-fusion core of the Human coronavirus 229E spike protein at 1.86 angstroem resolution.
SourceActa Crystallogr. D. Struct. Biol. 74:841-851(2018).
PubMed ID30198895
DOI10.1107/S2059798318008318

E1Titlehttps://viralzone.expasy.org/30?outline=all_by_species



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