A Trimerizing GxxxG Motif Is Uniquely Inserted in the Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Protein Transmembrane Domain†
Identifieur interne : 004102 ( Main/Exploration ); précédent : 004101; suivant : 004103A Trimerizing GxxxG Motif Is Uniquely Inserted in the Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Protein Transmembrane Domain†
Auteurs : Eyal Arbely [Israël] ; Zvi Granot [Israël] ; Itamar Kass [Israël] ; Joseph Orly [Israël] ; Isaiah T. Arkin [Israël]Source :
- Biochemistry [ 0006-2960 ] ; 2006.
Descripteurs français
- KwdFr :
- Alignement de séquences, Bactéries (métabolisme), Chloramphenicol O-acetyltransferase (métabolisme), Données de séquences moléculaires, Glycine (), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Humains, Membrane cellulaire (métabolisme), Modèles moléculaires, Motifs d'acides aminés, Protéines de l'enveloppe virale (), Structure quaternaire des protéines, Structure tertiaire des protéines, Séquence d'acides aminés, Test de complémentation, Virus du SRAS ().
- MESH :
- métabolisme : Bactéries, Chloramphenicol O-acetyltransferase, Membrane cellulaire.
- Alignement de séquences, Données de séquences moléculaires, Glycine, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Modèles moléculaires, Motifs d'acides aminés, Protéines de l'enveloppe virale, Structure quaternaire des protéines, Structure tertiaire des protéines, Séquence d'acides aminés, Test de complémentation, Virus du SRAS.
English descriptors
- KwdEn :
- Amino Acid Motifs, Amino Acid Sequence, Bacteria (metabolism), Cell Membrane (metabolism), Chloramphenicol O-Acetyltransferase (metabolism), Genetic Complementation Test, Glycine (chemistry), Humans, Membrane Glycoproteins (chemistry), Models, Molecular, Molecular Sequence Data, Protein Structure, Quaternary, Protein Structure, Tertiary, SARS Virus (chemistry), Sequence Alignment, Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (chemistry).
- MESH :
- chemical , chemistry : Glycine, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Chloramphenicol O-Acetyltransferase.
- chemistry : SARS Virus.
- metabolism : Bacteria, Cell Membrane.
- Amino Acid Motifs, Amino Acid Sequence, Genetic Complementation Test, Humans, Models, Molecular, Molecular Sequence Data, Protein Structure, Quaternary, Protein Structure, Tertiary, Sequence Alignment, Spike Glycoprotein, Coronavirus.
Abstract
In an attempt to understand what distinguishes severe acute respiratory syndrome (SARS) coronavirus (SCoV) from other members of the coronaviridae, we searched for elements that are unique to its proteins and not present in any other family member. We identified an insertion of two glycine residues, forming the GxxxG motif, in the SCoV spike protein transmembrane domain (TMD), which is not found in any other coronavirus. This surprising finding raises an “oligomerization riddle”: the GxxxG motif is a known dimerization signal, while the SCoV spike protein is known to be trimeric. Using an in vivo assay, we found that the SCoV spike protein TMD is oligomeric and that this oligomerization is driven by the GxxxG motif. We also found that the GxxxG motif contributes toward the trimerization of the entire spike protein; in that, mutations in the GxxxG motif decrease trimerization of the full-length protein expressed in mammalian cells. Using molecular modeling, we show that the SCoV spike protein TMD adopts a distinct and unique structure as opposed to all other coronaviruses. In this unique structure, the glycine residues of the GxxxG motif are facing each other, enhancing helix−helix interactions by allowing for the close positioning of the helices. This unique orientation of the glycine residues also stabilizes the trimeric bundle during multi-nanosecond molecular dynamics simulation in a hydrated lipid bilayer. To the best of our knowledge, this is the first demonstration that the GxxxG motif can potentiate other oligomeric forms beside a dimer. Finally, according to recent studies, the stabilization of the trimeric bundle is linked to a higher fusion activity of the spike protein, and the possible influence of the GxxxG motif on this feature is discussed.
Url:
DOI: 10.1021/bi060953v
Affiliations:
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Safra Campus, Givat-Ram, Jerusalem 91904</wicri:regionArea><wicri:noRegion>Jerusalem 91904</wicri:noRegion></affiliation></author><author><name sortKey="Kass, Itamar" sort="Kass, Itamar" uniqKey="Kass I" first="Itamar" last="Kass">Itamar Kass</name><affiliation wicri:level="1"><country xml:lang="fr">Israël</country><wicri:regionArea>The Alexander Silberman Institute of Life Sciences, Department of Biological Chemistry, The Hebrew University of Jerusalem,Edmond J. Safra Campus, Givat-Ram, Jerusalem 91904</wicri:regionArea><wicri:noRegion>Jerusalem 91904</wicri:noRegion></affiliation></author><author><name sortKey="Orly, Joseph" sort="Orly, Joseph" uniqKey="Orly J" first="Joseph" last="Orly">Joseph Orly</name><affiliation wicri:level="1"><country xml:lang="fr">Israël</country><wicri:regionArea>The Alexander Silberman Institute of Life Sciences, Department of Biological Chemistry, The Hebrew University of Jerusalem,Edmond J. Safra Campus, Givat-Ram, Jerusalem 91904</wicri:regionArea><wicri:noRegion>Jerusalem 91904</wicri:noRegion></affiliation></author><author><name sortKey="Arkin, Isaiah T" sort="Arkin, Isaiah T" uniqKey="Arkin I" first="Isaiah T." last="Arkin">Isaiah T. Arkin</name><affiliation wicri:level="1"><country xml:lang="fr">Israël</country><wicri:regionArea>The Alexander Silberman Institute of Life Sciences, Department of Biological Chemistry, The Hebrew University of Jerusalem,Edmond J. Safra Campus, Givat-Ram, Jerusalem 91904</wicri:regionArea><wicri:noRegion>Jerusalem 91904</wicri:noRegion></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Biochemistry</title><title level="j" type="abbrev">Biochemistry</title><idno type="ISSN">0006-2960</idno><idno type="eISSN">1520-4995</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published">2006</date><date type="published">2006</date><biblScope unit="vol">45</biblScope><biblScope unit="issue">38</biblScope><biblScope unit="page" from="11349">11349</biblScope><biblScope unit="page" to="11356">11356</biblScope></imprint><idno type="ISSN">0006-2960</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-2960</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Sequence</term><term>Bacteria (metabolism)</term><term>Cell Membrane (metabolism)</term><term>Chloramphenicol O-Acetyltransferase (metabolism)</term><term>Genetic Complementation Test</term><term>Glycine (chemistry)</term><term>Humans</term><term>Membrane Glycoproteins (chemistry)</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protein Structure, Quaternary</term><term>Protein Structure, Tertiary</term><term>SARS Virus (chemistry)</term><term>Sequence Alignment</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Alignement de séquences</term><term>Bactéries (métabolisme)</term><term>Chloramphenicol O-acetyltransferase (métabolisme)</term><term>Données de séquences moléculaires</term><term>Glycine ()</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Humains</term><term>Membrane cellulaire (métabolisme)</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Protéines de l'enveloppe virale ()</term><term>Structure quaternaire des protéines</term><term>Structure tertiaire des protéines</term><term>Séquence d'acides aminés</term><term>Test de complémentation</term><term>Virus du SRAS ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Glycine</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Chloramphenicol O-Acetyltransferase</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Bacteria</term><term>Cell Membrane</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Bactéries</term><term>Chloramphenicol O-acetyltransferase</term><term>Membrane cellulaire</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Sequence</term><term>Genetic Complementation Test</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protein Structure, Quaternary</term><term>Protein Structure, Tertiary</term><term>Sequence Alignment</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Alignement de séquences</term><term>Données de séquences moléculaires</term><term>Glycine</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Humains</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Protéines de l'enveloppe virale</term><term>Structure quaternaire des protéines</term><term>Structure tertiaire des protéines</term><term>Séquence d'acides aminés</term><term>Test de complémentation</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">In an attempt to understand what distinguishes severe acute respiratory syndrome (SARS) coronavirus (SCoV) from other members of the coronaviridae, we searched for elements that are unique to its proteins and not present in any other family member. We identified an insertion of two glycine residues, forming the GxxxG motif, in the SCoV spike protein transmembrane domain (TMD), which is not found in any other coronavirus. This surprising finding raises an “oligomerization riddle”: the GxxxG motif is a known dimerization signal, while the SCoV spike protein is known to be trimeric. Using an in vivo assay, we found that the SCoV spike protein TMD is oligomeric and that this oligomerization is driven by the GxxxG motif. We also found that the GxxxG motif contributes toward the trimerization of the entire spike protein; in that, mutations in the GxxxG motif decrease trimerization of the full-length protein expressed in mammalian cells. Using molecular modeling, we show that the SCoV spike protein TMD adopts a distinct and unique structure as opposed to all other coronaviruses. In this unique structure, the glycine residues of the GxxxG motif are facing each other, enhancing helix−helix interactions by allowing for the close positioning of the helices. This unique orientation of the glycine residues also stabilizes the trimeric bundle during multi-nanosecond molecular dynamics simulation in a hydrated lipid bilayer. To the best of our knowledge, this is the first demonstration that the GxxxG motif can potentiate other oligomeric forms beside a dimer. Finally, according to recent studies, the stabilization of the trimeric bundle is linked to a higher fusion activity of the spike protein, and the possible influence of the GxxxG motif on this feature is discussed.</div></front></TEI><affiliations><list><country><li>Israël</li></country></list><tree><country name="Israël"><noRegion><name sortKey="Arbely, Eyal" sort="Arbely, Eyal" uniqKey="Arbely E" first="Eyal" last="Arbely">Eyal Arbely</name></noRegion><name sortKey="Arkin, Isaiah T" sort="Arkin, Isaiah T" uniqKey="Arkin I" first="Isaiah T." last="Arkin">Isaiah T. Arkin</name><name sortKey="Granot, Zvi" sort="Granot, Zvi" uniqKey="Granot Z" first="Zvi" last="Granot">Zvi Granot</name><name sortKey="Kass, Itamar" sort="Kass, Itamar" uniqKey="Kass I" first="Itamar" last="Kass">Itamar Kass</name><name sortKey="Orly, Joseph" sort="Orly, Joseph" uniqKey="Orly J" first="Joseph" last="Orly">Joseph Orly</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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