HTTP 200 OK
Allow: GET, HEAD
Content-Type: application/json
InterPro-Version: 108.0
InterPro-Version-Minor: 0
Vary: Accept
{
"metadata": {
"accession": "cd22376",
"entry_id": null,
"type": "domain",
"go_terms": null,
"source_database": "cdd",
"member_databases": null,
"integrated": null,
"hierarchy": null,
"name": {
"name": "SD-1 and SD-2 subdomains, the S1/S2 cleavage region, and the S2 fusion subunit of the spike (S) glycoprotein from Porcine epidemic diarrhea virus and related alphacoronavirus",
"short": "PDEV-like_Spike_SD1-2_S1-2_S2"
},
"description": [
{
"text": "<p>This group contains the SD-1 and SD-2 subdomains of the S1 subunit C-terminal domain (C-domain), the S1/S2 cleavage region, and the S2 fusion subunit of the spike (S) glycoprotein from alphacoronaviruses, including porcine epidemic diarrhea virus (PEDV), Scotophilus bat coronavirus, and swine enteric coronavirus, among others. The CoV S protein is an envelope glycoprotein that plays a very important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains the coronavirus fusion machinery and is primarily alpha-helical. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-domain. The S1 C-domain also contains two subdomains (SD-1 and SD-2), which connect the S1 and S2 subunits. Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs, including SARS-CoV-2, SARS-CoV and MERS-CoV use the C-domain to bind their receptors. The S2 subunit comprises the fusion peptide (FP), a second proteolytic site (S2'), followed by an internal fusion peptide (IFP) and two heptad-repeat domains (HR1 and HR2) preceding the transmembrane domain (TM). After binding of the S1 subunit RBD on the virion to its receptor on the target cell, the HR1 and HR2 domains interact with each other to form a six-helix bundle (6-HB) fusion core, bringing viral and cellular membranes into close proximity for fusion and infection. In order to catalyze the membrane fusion reaction, CoV S needs to be primed through cleavage at the S1/S2 and S2' sites. In the case of human-infecting coronaviruses such as SARS-CoV-2, HCoV-OC43, MERS-CoV, and HKU1 the spike protein contains an insertion of (R/K)-(2X)n-(R/K) (furin cleavage motif) at the S1/S2 site, which is absent in SARS-CoV and other SARS-related coronaviruses, as well as Rousettus bat coronavirus HKU9. The region modeled in this cd (SD-1 and SD-2, the S1/S2 cleavage region, and the S2 fusion subunit) plays an essential role in viral entry by initiating fusion of the viral and cellular membranes. [[cite:PUB00147165], [cite:PUB00150662], [cite:PUB00094415], [cite:PUB00147166], [cite:PUB00147167], [cite:PUB00147168], [cite:PUB00095909], [cite:PUB00147169], [cite:PUB00107376], [cite:PUB00038186], [cite:PUB00147170], [cite:PUB00147171], [cite:PUB00147172], [cite:PUB00094064], [cite:PUB00147173], [cite:PUB00147174], [cite:PUB00107634], [cite:PUB00095914], [cite:PUB00097564]]</p>",
"llm": false,
"checked": false,
"updated": false
}
],
"wikipedia": null,
"literature": {
"PUB00147167": {
"PMID": 30989115,
"ISBN": null,
"volume": "5",
"issue": "4",
"year": 2019,
"title": "A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike.",
"URL": null,
"raw_pages": "eaav4580",
"medline_journal": "Sci Adv",
"ISO_journal": "Sci Adv",
"authors": [
"Xia S",
"Yan L",
"Xu W",
"Agrawal AS",
"Algaissi A",
"Tseng CK",
"Wang Q",
"Du L",
"Tan W",
"Wilson IA",
"Jiang S",
"Yang B",
"Lu L."
],
"DOI_URL": null
},
"PUB00147170": {
"PMID": 15518555,
"ISBN": null,
"volume": "43",
"issue": "44",
"year": 2004,
"title": "Characterization of the heptad repeat regions, HR1 and HR2, and design of a fusion core structure model of the spike protein from severe acute respiratory syndrome (SARS) coronavirus.",
"URL": null,
"raw_pages": "14064-71",
"medline_journal": "Biochemistry",
"ISO_journal": "Biochemistry",
"authors": [
"Xu Y",
"Zhu J",
"Liu Y",
"Lou Z",
"Yuan F",
"Liu Y",
"Cole DK",
"Ni L",
"Su N",
"Qin L",
"Li X",
"Bai Z",
"Bell JI",
"Pang H",
"Tien P",
"Gao GF",
"Rao Z."
],
"DOI_URL": null
},
"PUB00147169": {
"PMID": 24473083,
"ISBN": null,
"volume": "5",
"issue": null,
"year": 2014,
"title": "Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor.",
"URL": null,
"raw_pages": "3067",
"medline_journal": "Nat Commun",
"ISO_journal": "Nat Commun",
"authors": [
"Lu L",
"Liu Q",
"Zhu Y",
"Chan KH",
"Qin L",
"Li Y",
"Wang Q",
"Chan JF",
"Du L",
"Yu F",
"Ma C",
"Ye S",
"Yuen KY",
"Zhang R",
"Jiang S."
],
"DOI_URL": null
},
"PUB00038186": {
"PMID": 15840526,
"ISBN": null,
"volume": "335",
"issue": "2",
"year": 2005,
"title": "Central ions and lateral asparagine/glutamine zippers stabilize the post-fusion hairpin conformation of the SARS coronavirus spike glycoprotein.",
"URL": null,
"raw_pages": "276-85",
"medline_journal": "Virology",
"ISO_journal": "Virology",
"authors": [
"Duquerroy S",
"Vigouroux A",
"Rottier PJ",
"Rey FA",
"Bosch BJ."
],
"DOI_URL": "http://dx.doi.org/10.1016/j.virol.2005.02.022"
},
"PUB00107634": {
"PMID": 32221306,
"ISBN": null,
"volume": "11",
"issue": "1",
"year": 2020,
"title": "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV.",
"URL": null,
"raw_pages": "1620",
"medline_journal": "Nat Commun",
"ISO_journal": "Nat Commun",
"authors": [
"Ou X",
"Liu Y",
"Lei X",
"Li P",
"Mi D",
"Ren L",
"Guo L",
"Guo R",
"Chen T",
"Hu J",
"Xiang Z",
"Mu Z",
"Chen X",
"Chen J",
"Hu K",
"Jin Q",
"Wang J",
"Qian Z."
],
"DOI_URL": null
},
"PUB00097564": {
"PMID": 32203189,
"ISBN": null,
"volume": "17",
"issue": "6",
"year": 2020,
"title": "Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine.",
"URL": null,
"raw_pages": "613-620",
"medline_journal": "Cell Mol Immunol",
"ISO_journal": "Cell Mol Immunol",
"authors": [
"Tai W",
"He L",
"Zhang X",
"Pu J",
"Voronin D",
"Jiang S",
"Zhou Y",
"Du L."
],
"DOI_URL": null
},
"PUB00095914": {
"PMID": 30102747,
"ISBN": null,
"volume": "14",
"issue": "8",
"year": 2018,
"title": "Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2.",
"URL": null,
"raw_pages": "e1007236",
"medline_journal": "PLoS Pathog",
"ISO_journal": "PLoS Pathog",
"authors": [
"Song W",
"Gui M",
"Wang X",
"Xiang Y."
],
"DOI_URL": null
},
"PUB00147168": {
"PMID": 29684066,
"ISBN": null,
"volume": "14",
"issue": "4",
"year": 2018,
"title": "Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins.",
"URL": null,
"raw_pages": "e1007009",
"medline_journal": "PLoS Pathog",
"ISO_journal": "PLoS Pathog",
"authors": [
"Shang J",
"Zheng Y",
"Yang Y",
"Liu C",
"Geng Q",
"Luo C",
"Zhang W",
"Li F."
],
"DOI_URL": null
},
"PUB00147171": {
"PMID": 15043961,
"ISBN": null,
"volume": "363",
"issue": "9413",
"year": 2004,
"title": "Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors.",
"URL": null,
"raw_pages": "938-47",
"medline_journal": "Lancet",
"ISO_journal": "Lancet",
"authors": [
"Liu S",
"Xiao G",
"Chen Y",
"He Y",
"Niu J",
"Escalante CR",
"Xiong H",
"Farmar J",
"Debnath AK",
"Tien P",
"Jiang S."
],
"DOI_URL": null
},
"PUB00095909": {
"PMID": 31160783,
"ISBN": null,
"volume": "26",
"issue": "6",
"year": 2019,
"title": "Structural basis for human coronavirus attachment to sialic acid receptors.",
"URL": null,
"raw_pages": "481-489",
"medline_journal": "Nat Struct Mol Biol",
"ISO_journal": "Nat Struct Mol Biol",
"authors": [
"Tortorici MA",
"Walls AC",
"Lang Y",
"Wang C",
"Li Z",
"Koerhuis D",
"Boons GJ",
"Bosch BJ",
"Rey FA",
"de Groot RJ",
"Veesler D."
],
"DOI_URL": null
},
"PUB00147172": {
"PMID": 32532959,
"ISBN": null,
"volume": "5",
"issue": "1",
"year": 2020,
"title": "The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin.",
"URL": null,
"raw_pages": "92",
"medline_journal": "Signal Transduct Target Ther",
"ISO_journal": "Signal Transduct Target Ther",
"authors": [
"Xia S",
"Lan Q",
"Su S",
"Wang X",
"Xu W",
"Liu Z",
"Zhu Y",
"Wang Q",
"Lu L",
"Jiang S."
],
"DOI_URL": null
},
"PUB00147174": {
"PMID": 32272173,
"ISBN": null,
"volume": "178",
"issue": null,
"year": 2020,
"title": "Coronavirus membrane fusion mechanism offers a potential target for antiviral development.",
"URL": null,
"raw_pages": "104792",
"medline_journal": "Antiviral Res",
"ISO_journal": "Antiviral Res",
"authors": [
"Tang T",
"Bidon M",
"Jaimes JA",
"Whittaker GR",
"Daniel S."
],
"DOI_URL": null
},
"PUB00094415": {
"PMID": 31534041,
"ISBN": null,
"volume": "93",
"issue": "23",
"year": 2019,
"title": "The 3.1-Angstrom Cryo-electron Microscopy Structure of the Porcine Epidemic Diarrhea Virus Spike Protein in the Prefusion Conformation.",
"URL": null,
"raw_pages": null,
"medline_journal": "J Virol",
"ISO_journal": "J. Virol.",
"authors": [
"Wrapp D",
"McLellan JS."
],
"DOI_URL": null
},
"PUB00147165": {
"PMID": 32231345,
"ISBN": null,
"volume": "30",
"issue": "4",
"year": 2020,
"title": "Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion.",
"URL": null,
"raw_pages": "343-355",
"medline_journal": "Cell Res",
"ISO_journal": "Cell Res",
"authors": [
"Xia S",
"Liu M",
"Wang C",
"Xu W",
"Lan Q",
"Feng S",
"Qi F",
"Bao L",
"Du L",
"Liu S",
"Qin C",
"Sun F",
"Shi Z",
"Zhu Y",
"Jiang S",
"Lu L."
],
"DOI_URL": null
},
"PUB00147173": {
"PMID": 32366695,
"ISBN": null,
"volume": "369",
"issue": "6501",
"year": 2020,
"title": "Site-specific glycan analysis of the SARS-CoV-2 spike.",
"URL": null,
"raw_pages": "330-333",
"medline_journal": "Science",
"ISO_journal": "Science",
"authors": [
"Watanabe Y",
"Allen JD",
"Wrapp D",
"McLellan JS",
"Crispin M."
],
"DOI_URL": null
},
"PUB00150662": {
"PMID": 29392870,
"ISBN": null,
"volume": "65",
"issue": "3",
"year": 2018,
"title": "Swine enteric coronavirus disease: A review of 4 years with porcine epidemic diarrhoea virus and porcine deltacoronavirus in the United States and Canada.",
"URL": null,
"raw_pages": "660-675",
"medline_journal": "Transbound Emerg Dis",
"ISO_journal": "Transbound Emerg Dis",
"authors": [
"Niederwerder MC",
"Hesse RA."
],
"DOI_URL": null
},
"PUB00147166": {
"PMID": 32376627,
"ISBN": null,
"volume": "94",
"issue": "14",
"year": 2020,
"title": "Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity. ",
"URL": null,
"raw_pages": "e00635-20",
"medline_journal": "J Virol",
"ISO_journal": "J Virol",
"authors": [
"Zhu Y",
"Yu D",
"Yan H",
"Chong H",
"He Y."
],
"DOI_URL": null
},
"PUB00094064": {
"PMID": 32057769,
"ISBN": null,
"volume": "176",
"issue": null,
"year": 2020,
"title": "The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade.",
"URL": null,
"raw_pages": "104742",
"medline_journal": "Antiviral Res",
"ISO_journal": "Antiviral Res.",
"authors": [
"Coutard B",
"Valle C",
"de Lamballerie X",
"Canard B",
"Seidah NG",
"Decroly E."
],
"DOI_URL": null
},
"PUB00107376": {
"PMID": 28807998,
"ISBN": null,
"volume": "114",
"issue": "35",
"year": 2017,
"title": "Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen.",
"URL": null,
"raw_pages": "E7348-E7357",
"medline_journal": "Proc Natl Acad Sci U S A",
"ISO_journal": "Proc Natl Acad Sci U S A",
"authors": [
"Pallesen J",
"Wang N",
"Corbett KS",
"Wrapp D",
"Kirchdoerfer RN",
"Turner HL",
"Cottrell CA",
"Becker MM",
"Wang L",
"Shi W",
"Kong WP",
"Andres EL",
"Kettenbach AN",
"Denison MR",
"Chappell JD",
"Graham BS",
"Ward AB",
"McLellan JS."
],
"DOI_URL": null
}
},
"set_info": {
"accession": "cl40439",
"name": "CoV_Spike_S1-S2_S2"
},
"overlaps_with": null,
"counters": {
"subfamilies": 0,
"domain_architectures": 0,
"interactions": 0,
"matches": 1952,
"pathways": 0,
"proteins": 1952,
"proteomes": 5,
"sets": 1,
"structural_models": {
"alphafold": 0,
"bfvd": 0
},
"structures": 8,
"taxa": 87
},
"entry_annotations": {},
"cross_references": {},
"is_llm": false,
"is_reviewed_llm": false,
"is_updated_llm": false,
"representative_structure": null
}
}
