Structure of a proteolytically resistant core from the severe acute respiratory syndrome coronavirus S2 fusion protein.
Identifieur interne : 005418 ( Main/Merge ); précédent : 005417; suivant : 005419Structure of a proteolytically resistant core from the severe acute respiratory syndrome coronavirus S2 fusion protein.
Auteurs : Vinit M. Supekar [Italie] ; Chiara Bruckmann ; Paolo Ingallinella ; Elisabetta Bianchi ; Antonello Pessi ; Andrea CarfíSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2004.
Descripteurs français
- KwdFr :
- Antigènes viraux (), Conformation des protéines, Cristallographie aux rayons X, Dimérisation, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (métabolisme), Membrane cellulaire (métabolisme), Modèles moléculaires, Mutation, Paramyxoviridae (métabolisme), Peptides (), Protéines de fusion virale (), Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (métabolisme), Similitude de séquences d'acides aminés, Structure secondaire des protéines, Structure tertiaire des protéines, Séquence conservée, Séquence d'acides aminés.
- MESH :
- métabolisme : Glycoprotéines membranaires, Membrane cellulaire, Paramyxoviridae, Protéines de l'enveloppe virale.
- Antigènes viraux, Conformation des protéines, Cristallographie aux rayons X, Dimérisation, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Modèles moléculaires, Mutation, Peptides, Protéines de fusion virale, Protéines de l'enveloppe virale, Similitude de séquences d'acides aminés, Structure secondaire des protéines, Structure tertiaire des protéines, Séquence conservée, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Antigens, Viral (chemistry), Cell Membrane (metabolism), Conserved Sequence, Crystallography, X-Ray, Dimerization, Membrane Glycoproteins (chemistry), Membrane Glycoproteins (metabolism), Models, Molecular, Molecular Sequence Data, Mutation, Paramyxoviridae (metabolism), Peptides (chemistry), Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (metabolism), Viral Fusion Proteins (chemistry).
- MESH :
- chemical , chemistry : Antigens, Viral, Membrane Glycoproteins, Peptides, Viral Envelope Proteins, Viral Fusion Proteins.
- metabolism : Cell Membrane, Membrane Glycoproteins, Paramyxoviridae, Viral Envelope Proteins.
- Amino Acid Sequence, Conserved Sequence, Crystallography, X-Ray, Dimerization, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Spike Glycoprotein, Coronavirus.
Abstract
A coronavirus (CoV) has recently been identified as the causative agent of the severe acute respiratory syndrome (SARS) in humans. CoVs enter target cells through fusion of viral and cellular membranes mediated by the viral envelope glycoprotein S. We have determined by x-ray crystallography the structure of a proteolytically stable core fragment from the heptad repeat (HR) regions HR1 and HR2 of the SARS-CoV S protein. We have also determined the structure of an HR1-HR2 S core fragment, containing a shorter HR1 peptide and a C-terminally longer HR2 peptide that extends up to the transmembrane region. In these structures, three HR1 helices form a parallel coiled-coil trimer, whereas three HR2 peptides pack in an oblique and antiparallel fashion into the coiled-coil hydrophobic grooves, adopting mixed extended and alpha-helical conformations as in postfusion paramyxoviruses F proteins structures. Our structure positions a previously proposed internal fusion peptide adjacent to the N-terminus of HR1. Peptides from the HR2 region of SARS-CoV S have been shown to inhibit viral entry and infection in vitro. The structures presented here can thus open the path to the design of small-molecule inhibitors of viral entry and candidate vaccine antigens against this virus.
DOI: 10.1073/pnas.0406128102
PubMed: 15604146
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pubmed:15604146Le document en format XML
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Supekar</name><affiliation wicri:level="1"><nlm:affiliation>Istituto di Ricerche di Biologia Molecolare P. Angeletti, Via Pontina Km 30,600, 00040 Pomezia (Rome), Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Istituto di Ricerche di Biologia Molecolare P. Angeletti, Via Pontina Km 30,600, 00040 Pomezia (Rome)</wicri:regionArea><wicri:noRegion>00040 Pomezia (Rome)</wicri:noRegion></affiliation></author><author><name sortKey="Bruckmann, Chiara" sort="Bruckmann, Chiara" uniqKey="Bruckmann C" first="Chiara" last="Bruckmann">Chiara Bruckmann</name></author><author><name sortKey="Ingallinella, Paolo" sort="Ingallinella, Paolo" uniqKey="Ingallinella P" first="Paolo" last="Ingallinella">Paolo Ingallinella</name></author><author><name sortKey="Bianchi, Elisabetta" sort="Bianchi, Elisabetta" uniqKey="Bianchi E" first="Elisabetta" last="Bianchi">Elisabetta Bianchi</name></author><author><name sortKey="Pessi, Antonello" sort="Pessi, Antonello" uniqKey="Pessi A" first="Antonello" last="Pessi">Antonello Pessi</name></author><author><name sortKey="Carfi, Andrea" sort="Carfi, Andrea" uniqKey="Carfi A" first="Andrea" last="Carfí">Andrea Carfí</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Antigens, Viral (chemistry)</term><term>Cell Membrane (metabolism)</term><term>Conserved Sequence</term><term>Crystallography, X-Ray</term><term>Dimerization</term><term>Membrane Glycoproteins (chemistry)</term><term>Membrane Glycoproteins (metabolism)</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Mutation</term><term>Paramyxoviridae (metabolism)</term><term>Peptides (chemistry)</term><term>Protein Conformation</term><term>Protein Structure, Secondary</term><term>Protein Structure, Tertiary</term><term>Sequence Homology, Amino Acid</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (metabolism)</term><term>Viral Fusion Proteins (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antigènes viraux ()</term><term>Conformation des protéines</term><term>Cristallographie aux rayons X</term><term>Dimérisation</term><term>Données de séquences moléculaires</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Membrane cellulaire (métabolisme)</term><term>Modèles moléculaires</term><term>Mutation</term><term>Paramyxoviridae (métabolisme)</term><term>Peptides ()</term><term>Protéines de fusion virale ()</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Similitude de séquences d'acides aminés</term><term>Structure secondaire des protéines</term><term>Structure tertiaire des protéines</term><term>Séquence conservée</term><term>Séquence d'acides aminés</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antigens, Viral</term><term>Membrane Glycoproteins</term><term>Peptides</term><term>Viral Envelope Proteins</term><term>Viral Fusion Proteins</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cell Membrane</term><term>Membrane Glycoproteins</term><term>Paramyxoviridae</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Membrane cellulaire</term><term>Paramyxoviridae</term><term>Protéines de l'enveloppe virale</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Conserved Sequence</term><term>Crystallography, X-Ray</term><term>Dimerization</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Mutation</term><term>Protein Conformation</term><term>Protein Structure, Secondary</term><term>Protein Structure, Tertiary</term><term>Sequence Homology, Amino Acid</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Antigènes viraux</term><term>Conformation des protéines</term><term>Cristallographie aux rayons X</term><term>Dimérisation</term><term>Données de séquences moléculaires</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Modèles moléculaires</term><term>Mutation</term><term>Peptides</term><term>Protéines de fusion virale</term><term>Protéines de l'enveloppe virale</term><term>Similitude de séquences d'acides aminés</term><term>Structure secondaire des protéines</term><term>Structure tertiaire des protéines</term><term>Séquence conservée</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A coronavirus (CoV) has recently been identified as the causative agent of the severe acute respiratory syndrome (SARS) in humans. CoVs enter target cells through fusion of viral and cellular membranes mediated by the viral envelope glycoprotein S. We have determined by x-ray crystallography the structure of a proteolytically stable core fragment from the heptad repeat (HR) regions HR1 and HR2 of the SARS-CoV S protein. We have also determined the structure of an HR1-HR2 S core fragment, containing a shorter HR1 peptide and a C-terminally longer HR2 peptide that extends up to the transmembrane region. In these structures, three HR1 helices form a parallel coiled-coil trimer, whereas three HR2 peptides pack in an oblique and antiparallel fashion into the coiled-coil hydrophobic grooves, adopting mixed extended and alpha-helical conformations as in postfusion paramyxoviruses F proteins structures. Our structure positions a previously proposed internal fusion peptide adjacent to the N-terminus of HR1. Peptides from the HR2 region of SARS-CoV S have been shown to inhibit viral entry and infection in vitro. The structures presented here can thus open the path to the design of small-molecule inhibitors of viral entry and candidate vaccine antigens against this virus.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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