Two-Step Conformational Changes in a Coronavirus Envelope Glycoprotein Mediated by Receptor Binding and Proteolysis
Identifieur interne : 002E95 ( Main/Exploration ); précédent : 002E94; suivant : 002E96Two-Step Conformational Changes in a Coronavirus Envelope Glycoprotein Mediated by Receptor Binding and Proteolysis
Auteurs : Shutoku Matsuyama [Japon] ; Fumihiro Taguchi [Japon]Source :
- Journal of virology [ 0022-538X ] ; 2009.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
The coronaviruses mouse hepatitis virus type 2 (MHV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) utilize proteases to enter host cells. Upon receptor binding, the spike (S) proteins of both viruses are activated for membrane fusion by proteases, such as trypsin, present in the environment, facilitating virus entry from the cell surface. In contrast, in the absence of extracellular proteases, these viruses can enter cells via an endosomal pathway and utilize endosomal cathepsins for S protein activation. We demonstrate that the MHV-2 S protein uses multistep conformational changes for membrane fusion. After interaction with a soluble form of the MHV receptor (CEACAM1a), the metastable form of S protein is converted to a stable trimer, as revealed by mildly denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Liposome-binding assays indicate that the receptor-bound virions are associated with the target membrane through hydrophobic interactions. The exposure of receptor-bound S protein to trypsin or cathepsin L (CPL) induces the formation of six-helix bundles (6HB), the final conformation. This trypsin- or CPL-mediated conversion to 6HB can be blocked by a heptad repeat peptide known to block the formation of 6HB. Although trypsin treatment enabled receptor-bound MHV-2 to enter from the cell surface, CPL failed to do so. Interestingly, consecutive treatment with CPL and then chlorpromazine enabled a portion of the virus to enter from cell surface. These results suggest that trypsin suffices for the induction of membrane fusion of receptor-primed S protein, but an additional unidentified cellular factor is required to trigger membrane fusion by CPL.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Two-Step Conformational Changes in a Coronavirus Envelope Glycoprotein Mediated by Receptor Binding and Proteolysis</title><author><name sortKey="Matsuyama, Shutoku" sort="Matsuyama, Shutoku" uniqKey="Matsuyama S" first="Shutoku" last="Matsuyama">Shutoku Matsuyama</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen</s1><s2>Musashi-Murayama, Tokyo 208-0011</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Taguchi, Fumihiro" sort="Taguchi, Fumihiro" uniqKey="Taguchi F" first="Fumihiro" last="Taguchi">Fumihiro Taguchi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen</s1><s2>Musashi-Murayama, Tokyo 208-0011</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">09-0437515</idno><date when="2009">2009</date><idno type="stanalyst">PASCAL 09-0437515 INIST</idno><idno type="RBID">Pascal:09-0437515</idno><idno type="wicri:Area/PascalFrancis/Corpus">000186</idno><idno type="wicri:Area/PascalFrancis/Curation">000802</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000172</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000172</idno><idno type="wicri:doubleKey">0022-538X:2009:Matsuyama S:two:step:conformational</idno><idno type="wicri:Area/Main/Merge">002F49</idno><idno type="wicri:Area/Main/Curation">002E95</idno><idno type="wicri:Area/Main/Exploration">002E95</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Two-Step Conformational Changes in a Coronavirus Envelope Glycoprotein Mediated by Receptor Binding and Proteolysis</title><author><name sortKey="Matsuyama, Shutoku" sort="Matsuyama, Shutoku" uniqKey="Matsuyama S" first="Shutoku" last="Matsuyama">Shutoku Matsuyama</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen</s1><s2>Musashi-Murayama, Tokyo 208-0011</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Taguchi, Fumihiro" sort="Taguchi, Fumihiro" uniqKey="Taguchi F" first="Fumihiro" last="Taguchi">Fumihiro Taguchi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen</s1><s2>Musashi-Murayama, Tokyo 208-0011</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biological receptor</term><term>Conformation</term><term>Coronavirus</term><term>Glycoprotein</term><term>Proteolysis</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term><term>Conformation</term><term>Glycoprotéine</term><term>Récepteur biologique</term><term>Protéolyse</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The coronaviruses mouse hepatitis virus type 2 (MHV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) utilize proteases to enter host cells. Upon receptor binding, the spike (S) proteins of both viruses are activated for membrane fusion by proteases, such as trypsin, present in the environment, facilitating virus entry from the cell surface. In contrast, in the absence of extracellular proteases, these viruses can enter cells via an endosomal pathway and utilize endosomal cathepsins for S protein activation. We demonstrate that the MHV-2 S protein uses multistep conformational changes for membrane fusion. After interaction with a soluble form of the MHV receptor (CEACAM1a), the metastable form of S protein is converted to a stable trimer, as revealed by mildly denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Liposome-binding assays indicate that the receptor-bound virions are associated with the target membrane through hydrophobic interactions. The exposure of receptor-bound S protein to trypsin or cathepsin L (CPL) induces the formation of six-helix bundles (6HB), the final conformation. This trypsin- or CPL-mediated conversion to 6HB can be blocked by a heptad repeat peptide known to block the formation of 6HB. Although trypsin treatment enabled receptor-bound MHV-2 to enter from the cell surface, CPL failed to do so. Interestingly, consecutive treatment with CPL and then chlorpromazine enabled a portion of the virus to enter from cell surface. These results suggest that trypsin suffices for the induction of membrane fusion of receptor-primed S protein, but an additional unidentified cellular factor is required to trigger membrane fusion by CPL.</div></front></TEI><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement></list><tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Matsuyama, Shutoku" sort="Matsuyama, Shutoku" uniqKey="Matsuyama S" first="Shutoku" last="Matsuyama">Shutoku Matsuyama</name></region><name sortKey="Taguchi, Fumihiro" sort="Taguchi, Fumihiro" uniqKey="Taguchi F" first="Fumihiro" last="Taguchi">Fumihiro Taguchi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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