Role of spike protein endodomains in regulating coronavirus entry.
Identifieur interne : 002A33 ( Main/Exploration ); précédent : 002A32; suivant : 002A34Role of spike protein endodomains in regulating coronavirus entry.
Auteurs : Ana Shulla [États-Unis] ; Tom GallagherSource :
- The Journal of biological chemistry [ 1083-351X ] ; 2009.
Descripteurs français
- KwdFr :
- Acide palmitique (), Animaux, Cellules HeLa, Coronavirus (pathogénicité), Cystéine (), Données de séquences moléculaires, Fibroblastes (métabolisme), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (physiologie), Humains, Liaison aux protéines, Lipides (), Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (physiologie), Souris, Structure tertiaire des protéines, Séquence d'acides aminés.
- MESH :
- métabolisme : Fibroblastes.
- pathogénicité : Coronavirus.
- physiologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- Acide palmitique, Animaux, Cellules HeLa, Cystéine, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Liaison aux protéines, Lipides, Protéines de l'enveloppe virale, Souris, Structure tertiaire des protéines, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Coronavirus (pathogenicity), Cysteine (chemistry), Fibroblasts (metabolism), HeLa Cells, Humans, Lipids (chemistry), Membrane Glycoproteins (chemistry), Membrane Glycoproteins (physiology), Mice, Molecular Sequence Data, Palmitic Acid (chemistry), Protein Binding, Protein Structure, Tertiary, Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (physiology).
- MESH :
- chemical , chemistry : Cysteine, Lipids, Membrane Glycoproteins, Palmitic Acid, Viral Envelope Proteins.
- metabolism : Fibroblasts.
- pathogenicity : Coronavirus.
- chemical , physiology : Membrane Glycoproteins, Viral Envelope Proteins.
- Amino Acid Sequence, Animals, HeLa Cells, Humans, Mice, Molecular Sequence Data, Protein Binding, Protein Structure, Tertiary, Spike Glycoprotein, Coronavirus.
Abstract
Enveloped viruses enter cells by viral glycoprotein-mediated binding to host cells and subsequent fusion of virus and host cell membranes. For the coronaviruses, viral spike (S) proteins execute these cell entry functions. The S proteins are set apart from other viral and cellular membrane fusion proteins by their extensively palmitoylated membrane-associated tails. Palmitate adducts are generally required for protein-mediated fusions, but their precise roles in the process are unclear. To obtain additional insights into the S-mediated membrane fusion process, we focused on these acylated carboxyl-terminal intravirion tails. Substituting alanines for the cysteines that are subject to palmitoylation had effects on both S incorporation into virions and S-mediated membrane fusions. In specifically dissecting the effects of endodomain mutations on the fusion process, we used antiviral heptad repeat peptides that bind only to folding intermediates in the S-mediated fusion process and found that mutants lacking three palmitoylated cysteines remained in transitional folding states nearly 10 times longer than native S proteins. This slower refolding was also reflected in the paucity of postfusion six-helix bundle configurations among the mutant S proteins. Viruses with fewer palmitoylated S protein cysteines entered cells slowly and had reduced specific infectivities. These findings indicate that lipid adducts anchoring S proteins into virus membranes are necessary for the rapid, productive S protein refolding events that culminate in membrane fusions. These studies reveal a previously unappreciated role for covalently attached lipids on the endodomains of viral proteins eliciting membrane fusion reactions.
DOI: 10.1074/jbc.M109.043547
PubMed: 19801669
Affiliations:
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Le document en format XML
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uniqKey="Shulla A" first="Ana" last="Shulla">Ana Shulla</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, Illinois 60153, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, Illinois 60153</wicri:regionArea><wicri:noRegion>Illinois 60153</wicri:noRegion></affiliation></author><author><name sortKey="Gallagher, Tom" sort="Gallagher, Tom" uniqKey="Gallagher T" first="Tom" last="Gallagher">Tom Gallagher</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Coronavirus 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(physiologie)</term><term>Humains</term><term>Liaison aux protéines</term><term>Lipides ()</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (physiologie)</term><term>Souris</term><term>Structure tertiaire des protéines</term><term>Séquence d'acides aminés</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cysteine</term><term>Lipids</term><term>Membrane Glycoproteins</term><term>Palmitic Acid</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Fibroblasts</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Fibroblastes</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>HeLa Cells</term><term>Humans</term><term>Mice</term><term>Molecular Sequence Data</term><term>Protein Binding</term><term>Protein Structure, Tertiary</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Acide palmitique</term><term>Animaux</term><term>Cellules HeLa</term><term>Cystéine</term><term>Données de séquences moléculaires</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Humains</term><term>Liaison aux protéines</term><term>Lipides</term><term>Protéines de l'enveloppe virale</term><term>Souris</term><term>Structure tertiaire des protéines</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Enveloped viruses enter cells by viral glycoprotein-mediated binding to host cells and subsequent fusion of virus and host cell membranes. For the coronaviruses, viral spike (S) proteins execute these cell entry functions. The S proteins are set apart from other viral and cellular membrane fusion proteins by their extensively palmitoylated membrane-associated tails. Palmitate adducts are generally required for protein-mediated fusions, but their precise roles in the process are unclear. To obtain additional insights into the S-mediated membrane fusion process, we focused on these acylated carboxyl-terminal intravirion tails. Substituting alanines for the cysteines that are subject to palmitoylation had effects on both S incorporation into virions and S-mediated membrane fusions. In specifically dissecting the effects of endodomain mutations on the fusion process, we used antiviral heptad repeat peptides that bind only to folding intermediates in the S-mediated fusion process and found that mutants lacking three palmitoylated cysteines remained in transitional folding states nearly 10 times longer than native S proteins. This slower refolding was also reflected in the paucity of postfusion six-helix bundle configurations among the mutant S proteins. Viruses with fewer palmitoylated S protein cysteines entered cells slowly and had reduced specific infectivities. These findings indicate that lipid adducts anchoring S proteins into virus membranes are necessary for the rapid, productive S protein refolding events that culminate in membrane fusions. These studies reveal a previously unappreciated role for covalently attached lipids on the endodomains of viral proteins eliciting membrane fusion reactions.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Gallagher, Tom" sort="Gallagher, Tom" uniqKey="Gallagher T" first="Tom" last="Gallagher">Tom Gallagher</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Shulla, Ana" sort="Shulla, Ana" uniqKey="Shulla A" first="Ana" last="Shulla">Ana Shulla</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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