SrasV1, Main, Exploration, bibRecord, 005587

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†

Identifieur interne : 005587 ( Main/Exploration ); précédent : 005586; suivant : 005588

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†

Auteurs : Yanhui Xu [Royaume-Uni] ; Jieqing Zhu [Royaume-Uni] ; Yiwei Liu [Royaume-Uni] ; Zhiyong Lou [Royaume-Uni] ; Fang Yuan [Royaume-Uni] ; Yueyong Liu [Royaume-Uni] ; David K. Cole [Royaume-Uni] ; Ling Ni [Royaume-Uni] ; Nan Su [Royaume-Uni] ; Lan Qin [Royaume-Uni] ; Xu Li [Royaume-Uni] ; Zhihong Bai [Royaume-Uni] ; John I. Bell [Royaume-Uni] ; Hai Pang [Royaume-Uni] ; Po Tien [Royaume-Uni] ; George F. Gao [Royaume-Uni] ; Zihe Rao [Royaume-Uni]

Source :

Biochemistry [ 0006-2960 ] ; 2004.

RBID : ISTEX:0F1E640EA336F1262CDA1D82616FB074D44E88DE

Descripteurs français

English descriptors

KwdEn :
- Amino Acid Sequence, Binding Sites (genetics), Computer Simulation, Genetic Vectors (chemical synthesis), Membrane Glycoproteins (chemical synthesis), Membrane Glycoproteins (genetics), Models, Molecular, Molecular Sequence Data, Murine hepatitis virus (chemistry), Murine hepatitis virus (genetics), Murine hepatitis virus (pathogenicity), Peptide Fragments (biosynthesis), Peptide Fragments (chemistry), Peptide Fragments (genetics), Peptides (chemistry), Peptides (genetics), Peptides (metabolism), Protein Binding (genetics), Protein Engineering (methods), Protein Structure, Secondary (genetics), Recombinant Fusion Proteins (chemical synthesis), Recombinant Fusion Proteins (genetics), Recombinant Fusion Proteins (metabolism), Repetitive Sequences, Amino Acid (genetics), SARS Virus (chemistry), SARS Virus (genetics), SARS Virus (pathogenicity), Solubility, Spike Glycoprotein, Coronavirus, Structural Homology, Protein, Viral Envelope Proteins (chemical synthesis), Viral Envelope Proteins (genetics), Viral Fusion Proteins (chemical synthesis), Viral Fusion Proteins (genetics), Viral Fusion Proteins (metabolism).
MESH :
- chemical , biosynthesis : Peptide Fragments.
- chemical , chemical synthesis : Membrane Glycoproteins, Recombinant Fusion Proteins, Viral Envelope Proteins, Viral Fusion Proteins.
- chemical synthesis : Genetic Vectors.
- chemistry : Murine hepatitis virus, Peptide Fragments, Peptides, SARS Virus.
- genetics : Binding Sites, Membrane Glycoproteins, Murine hepatitis virus, Peptide Fragments, Peptides, Protein Binding, Protein Structure, Secondary, Recombinant Fusion Proteins, Repetitive Sequences, Amino Acid, SARS Virus, Viral Envelope Proteins, Viral Fusion Proteins.
- chemical , metabolism : Peptides, Recombinant Fusion Proteins, Viral Fusion Proteins.
- methods : Protein Engineering.
- pathogenicity : Murine hepatitis virus, SARS Virus.
- Amino Acid Sequence, Computer Simulation, Models, Molecular, Molecular Sequence Data, Solubility, Spike Glycoprotein, Coronavirus, Structural Homology, Protein.

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emergent virus responsible for a worldwide epidemic in 2003. The coronavirus spike proteins belong to class I fusion proteins, and are characterized by the existence of two heptad repeat (HR) regions, HR1 and HR2. The HR1 region in coronaviruses is predicted to be considerably longer than that in other type I virus fusion proteins. Therefore the exact binding sequence to HR2 from the HR1 is not clear. In this study, we defined the region of HR1 that binds to HR2 by a series of biochemical and biophysical measures. Subsequently the defined HR1 (902−952) and HR2 (1145−1184) chains, which are different from previously defined binding regions, were linked together by a flexible linker to form a single-chain construct, 2-Helix. This protein was expressed in Escherichia coli and forms a typical six-helix coiled coil bundle. Highly conserved HR regions between mouse hepatitis virus (MHV) and SARS-CoV spike proteins suggest a similar three-dimensional structure for the two fusion cores. Here, we constructed a homology model for SARS coronavirus fusion core based on our biochemical analysis and determined the MHV fusion core structure. We also propose an important target site for fusion inhibitor design and several strategies, which have been successfully used in fusion inhibitor design for human immunodeficiency virus (HIV), for the treatment of SARS infection.

Url:

https://api.istex.fr/ark:/67375/TPS-57BCB3PS-Z/fulltext.pdf

DOI: 10.1021/bi049101q

Affiliations:

Royaume-Uni

Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Binding Sites (genetics)</term>
<term>Computer Simulation</term>
<term>Genetic Vectors (chemical synthesis)</term>
<term>Membrane Glycoproteins (chemical synthesis)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Murine hepatitis virus (chemistry)</term>
<term>Murine hepatitis virus (genetics)</term>
<term>Murine hepatitis virus (pathogenicity)</term>
<term>Peptide Fragments (biosynthesis)</term>
<term>Peptide Fragments (chemistry)</term>
<term>Peptide Fragments (genetics)</term>
<term>Peptides (chemistry)</term>
<term>Peptides (genetics)</term>
<term>Peptides (metabolism)</term>
<term>Protein Binding (genetics)</term>
<term>Protein Engineering (methods)</term>
<term>Protein Structure, Secondary (genetics)</term>
<term>Recombinant Fusion Proteins (chemical synthesis)</term>
<term>Recombinant Fusion Proteins (genetics)</term>
<term>Recombinant Fusion Proteins (metabolism)</term>
<term>Repetitive Sequences, Amino Acid (genetics)</term>
<term>SARS Virus (chemistry)</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (pathogenicity)</term>
<term>Solubility</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Structural Homology, Protein</term>
<term>Viral Envelope Proteins (chemical synthesis)</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Fusion Proteins (chemical synthesis)</term>
<term>Viral Fusion Proteins (genetics)</term>
<term>Viral Fusion Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Données de séquences moléculaires</term>
<term>Fragments peptidiques ()</term>
<term>Fragments peptidiques (biosynthèse)</term>
<term>Fragments peptidiques (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (synthèse chimique)</term>
<term>Ingénierie des protéines ()</term>
<term>Liaison aux protéines (génétique)</term>
<term>Modèles moléculaires</term>
<term>Peptides ()</term>
<term>Peptides (génétique)</term>
<term>Peptides (métabolisme)</term>
<term>Protéines de fusion recombinantes (génétique)</term>
<term>Protéines de fusion recombinantes (métabolisme)</term>
<term>Protéines de fusion recombinantes (synthèse chimique)</term>
<term>Protéines de fusion virale (génétique)</term>
<term>Protéines de fusion virale (métabolisme)</term>
<term>Protéines de fusion virale (synthèse chimique)</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (synthèse chimique)</term>
<term>Similitude structurale de protéines</term>
<term>Simulation numérique</term>
<term>Sites de fixation (génétique)</term>
<term>Solubilité</term>
<term>Structure secondaire des protéines (génétique)</term>
<term>Séquence d'acides aminés</term>
<term>Séquences répétées d'acides aminés (génétique)</term>
<term>Vecteurs génétiques (synthèse chimique)</term>
<term>Virus de l'hépatite murine ()</term>
<term>Virus de l'hépatite murine (génétique)</term>
<term>Virus de l'hépatite murine (pathogénicité)</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (pathogénicité)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Peptide Fragments</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Membrane Glycoproteins</term>
<term>Recombinant Fusion Proteins</term>
<term>Viral Envelope Proteins</term>
<term>Viral Fusion Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Fragments peptidiques</term>
</keywords>
<keywords scheme="MESH" qualifier="chemical synthesis" xml:lang="en"><term>Genetic Vectors</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Murine hepatitis virus</term>
<term>Peptide Fragments</term>
<term>Peptides</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Binding Sites</term>
<term>Membrane Glycoproteins</term>
<term>Murine hepatitis virus</term>
<term>Peptide Fragments</term>
<term>Peptides</term>
<term>Protein Binding</term>
<term>Protein Structure, Secondary</term>
<term>Recombinant Fusion Proteins</term>
<term>Repetitive Sequences, Amino Acid</term>
<term>SARS Virus</term>
<term>Viral Envelope Proteins</term>
<term>Viral Fusion Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Liaison aux protéines</term>
<term>Peptides</term>
<term>Protéines de fusion recombinantes</term>
<term>Protéines de fusion virale</term>
<term>Protéines de l'enveloppe virale</term>
<term>Sites de fixation</term>
<term>Structure secondaire des protéines</term>
<term>Séquences répétées d'acides aminés</term>
<term>Virus de l'hépatite murine</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Peptides</term>
<term>Recombinant Fusion Proteins</term>
<term>Viral Fusion Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Protein Engineering</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Peptides</term>
<term>Protéines de fusion recombinantes</term>
<term>Protéines de fusion virale</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Murine hepatitis virus</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus de l'hépatite murine</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Glycoprotéines membranaires</term>
<term>Protéines de fusion recombinantes</term>
<term>Protéines de fusion virale</term>
<term>Protéines de l'enveloppe virale</term>
<term>Vecteurs génétiques</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Computer Simulation</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Solubility</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Structural Homology, Protein</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Données de séquences moléculaires</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Ingénierie des protéines</term>
<term>Modèles moléculaires</term>
<term>Peptides</term>
<term>Similitude structurale de protéines</term>
<term>Simulation numérique</term>
<term>Solubilité</term>
<term>Séquence d'acides aminés</term>
<term>Virus de l'hépatite murine</term>
<term>Virus du SRAS</term>
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<front><div type="abstract">Severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emergent virus responsible for a worldwide epidemic in 2003. The coronavirus spike proteins belong to class I fusion proteins, and are characterized by the existence of two heptad repeat (HR) regions, HR1 and HR2. The HR1 region in coronaviruses is predicted to be considerably longer than that in other type I virus fusion proteins. Therefore the exact binding sequence to HR2 from the HR1 is not clear. In this study, we defined the region of HR1 that binds to HR2 by a series of biochemical and biophysical measures. Subsequently the defined HR1 (902−952) and HR2 (1145−1184) chains, which are different from previously defined binding regions, were linked together by a flexible linker to form a single-chain construct, 2-Helix. This protein was expressed in Escherichia coli and forms a typical six-helix coiled coil bundle. Highly conserved HR regions between mouse hepatitis virus (MHV) and SARS-CoV spike proteins suggest a similar three-dimensional structure for the two fusion cores. Here, we constructed a homology model for SARS coronavirus fusion core based on our biochemical analysis and determined the MHV fusion core structure. We also propose an important target site for fusion inhibitor design and several strategies, which have been successfully used in fusion inhibitor design for human immunodeficiency virus (HIV), for the treatment of SARS infection.</div>
</front>
</TEI>
<affiliations><list><country><li>Royaume-Uni</li>
</country>
</list>
<tree><country name="Royaume-Uni"><noRegion><name sortKey="Xu, Yanhui" sort="Xu, Yanhui" uniqKey="Xu Y" first="Yanhui" last="Xu">Yanhui Xu</name>
</noRegion>
<name sortKey="Bai, Zhihong" sort="Bai, Zhihong" uniqKey="Bai Z" first="Zhihong" last="Bai">Zhihong Bai</name>
<name sortKey="Bell, John I" sort="Bell, John I" uniqKey="Bell J" first="John I." last="Bell">John I. Bell</name>
<name sortKey="Cole, David K" sort="Cole, David K" uniqKey="Cole D" first="David K." last="Cole">David K. Cole</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<name sortKey="Li, Xu" sort="Li, Xu" uniqKey="Li X" first="Xu" last="Li">Xu Li</name>
<name sortKey="Liu, Yiwei" sort="Liu, Yiwei" uniqKey="Liu Y" first="Yiwei" last="Liu">Yiwei Liu</name>
<name sortKey="Liu, Yueyong" sort="Liu, Yueyong" uniqKey="Liu Y" first="Yueyong" last="Liu">Yueyong Liu</name>
<name sortKey="Lou, Zhiyong" sort="Lou, Zhiyong" uniqKey="Lou Z" first="Zhiyong" last="Lou">Zhiyong Lou</name>
<name sortKey="Ni, Ling" sort="Ni, Ling" uniqKey="Ni L" first="Ling" last="Ni">Ling Ni</name>
<name sortKey="Pang, Hai" sort="Pang, Hai" uniqKey="Pang H" first="Hai" last="Pang">Hai Pang</name>
<name sortKey="Qin, Lan" sort="Qin, Lan" uniqKey="Qin L" first="Lan" last="Qin">Lan Qin</name>
<name sortKey="Rao, Zihe" sort="Rao, Zihe" uniqKey="Rao Z" first="Zihe" last="Rao">Zihe Rao</name>
<name sortKey="Su, Nan" sort="Su, Nan" uniqKey="Su N" first="Nan" last="Su">Nan Su</name>
<name sortKey="Tien, Po" sort="Tien, Po" uniqKey="Tien P" first="Po" last="Tien">Po Tien</name>
<name sortKey="Yuan, Fang" sort="Yuan, Fang" uniqKey="Yuan F" first="Fang" last="Yuan">Fang Yuan</name>
<name sortKey="Zhu, Jieqing" sort="Zhu, Jieqing" uniqKey="Zhu J" first="Jieqing" last="Zhu">Jieqing Zhu</name>
</country>
</tree>
</affiliations>
</record>

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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†

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†

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