SrasV1, Main, Exploration, bibRecord, 000F61

Pre-fusion structure of a human coronavirus spike protein.

Identifieur interne : 000F61 ( Main/Exploration ); précédent : 000F60; suivant : 000F62

Pre-fusion structure of a human coronavirus spike protein.

Auteurs : Robert N. Kirchdoerfer [États-Unis] ; Christopher A. Cottrell [États-Unis] ; Nianshuang Wang [États-Unis] ; Jesper Pallesen [États-Unis] ; Hadi M. Yassine [États-Unis] ; Hannah L. Turner [États-Unis] ; Kizzmekia S. Corbett [États-Unis] ; Barney S. Graham [États-Unis] ; Jason S. Mclellan [États-Unis] ; Andrew B. Ward [États-Unis]

Source :

Nature [ 1476-4687 ] ; 2016.

RBID : pubmed:26935699

Descripteurs français

English descriptors

KwdEn :
- Cell Line, Coronavirus (chemistry), Coronavirus (ultrastructure), Cryoelectron Microscopy, Humans, Membrane Fusion, Models, Molecular, Protein Binding, Protein Multimerization, Protein Structure, Quaternary, Protein Structure, Tertiary, Protein Subunits (chemistry), Protein Subunits (metabolism), Proteolysis, Receptors, Virus (metabolism), Spike Glycoprotein, Coronavirus (chemistry), Spike Glycoprotein, Coronavirus (metabolism), Spike Glycoprotein, Coronavirus (ultrastructure), Viral Vaccines (chemistry), Viral Vaccines (immunology), Virus Internalization.
MESH :
- chemical , chemistry : Protein Subunits, Spike Glycoprotein, Coronavirus, Viral Vaccines.
- chemistry : Coronavirus.
- chemical , immunology : Viral Vaccines.
- chemical , metabolism : Protein Subunits, Receptors, Virus, Spike Glycoprotein, Coronavirus.
- ultrastructure : Coronavirus, Spike Glycoprotein, Coronavirus.
- Cell Line, Cryoelectron Microscopy, Humans, Membrane Fusion, Models, Molecular, Protein Binding, Protein Multimerization, Protein Structure, Quaternary, Protein Structure, Tertiary, Proteolysis, Virus Internalization.

Abstract

HKU1 is a human betacoronavirus that causes mild yet prevalent respiratory disease, and is related to the zoonotic SARS and MERS betacoronaviruses, which have high fatality rates and pandemic potential. Cell tropism and host range is determined in part by the coronavirus spike (S) protein, which binds cellular receptors and mediates membrane fusion. As the largest known class I fusion protein, its size and extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions. Here we present the 4.0 Å resolution structure of the trimeric HKU1 S protein determined using single-particle cryo-electron microscopy. In the pre-fusion conformation, the receptor-binding subunits, S1, rest above the fusion-mediating subunits, S2, preventing their conformational rearrangement. Surprisingly, the S1 C-terminal domains are interdigitated and form extensive quaternary interactions that occlude surfaces known in other coronaviruses to bind protein receptors. These features, along with the location of the two protease sites known to be important for coronavirus entry, provide a structural basis to support a model of membrane fusion mediated by progressive S protein destabilization through receptor binding and proteolytic cleavage. These studies should also serve as a foundation for the structure-based design of betacoronavirus vaccine immunogens.

DOI: 10.1038/nature17200
PubMed: 26935699

Affiliations:

États-Unis

Le document en format XML

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<front><div type="abstract" xml:lang="en">HKU1 is a human betacoronavirus that causes mild yet prevalent respiratory disease, and is related to the zoonotic SARS and MERS betacoronaviruses, which have high fatality rates and pandemic potential. Cell tropism and host range is determined in part by the coronavirus spike (S) protein, which binds cellular receptors and mediates membrane fusion. As the largest known class I fusion protein, its size and extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions. Here we present the 4.0 Å resolution structure of the trimeric HKU1 S protein determined using single-particle cryo-electron microscopy. In the pre-fusion conformation, the receptor-binding subunits, S1, rest above the fusion-mediating subunits, S2, preventing their conformational rearrangement. Surprisingly, the S1 C-terminal domains are interdigitated and form extensive quaternary interactions that occlude surfaces known in other coronaviruses to bind protein receptors. These features, along with the location of the two protease sites known to be important for coronavirus entry, provide a structural basis to support a model of membrane fusion mediated by progressive S protein destabilization through receptor binding and proteolytic cleavage. These studies should also serve as a foundation for the structure-based design of betacoronavirus vaccine immunogens. </div>
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</record>

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EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000F61 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000F61 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    SrasV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:26935699
   |texte=   Pre-fusion structure of a human coronavirus spike protein.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:26935699" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a SrasV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Apr 28 14:49:16 2020. Site generation: Sat Mar 27 22:06:49 2021

Serveur d'exploration SRAS

Pre-fusion structure of a human coronavirus spike protein.

Pre-fusion structure of a human coronavirus spike protein.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	Serveur d'exploration SRAS
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.