Two-step conformational changes in a coronavirus envelope glycoprotein mediated by receptor binding and proteolysis.
Identifieur interne : 002981 ( Main/Exploration ); précédent : 002980; suivant : 002982Two-step conformational changes in a coronavirus envelope glycoprotein mediated by receptor binding and proteolysis.
Auteurs : Shutoku Matsuyama [Japon] ; Fumihiro TaguchiSource :
- Journal of virology [ 1098-5514 ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Antigène carcinoembryonnaire (métabolisme), Cathepsines (métabolisme), Conformation des protéines, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (métabolisme), Liaison aux protéines, Liposomes (métabolisme), Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (métabolisme), Pénétration virale, Souris, Trypsine (métabolisme), Virus de l'hépatite murine (métabolisme).
- MESH :
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- métabolisme : Antigène carcinoembryonnaire, Cathepsines, Glycoprotéines membranaires, Liposomes, Protéines de l'enveloppe virale, Trypsine, Virus de l'hépatite murine.
- Animaux, Conformation des protéines, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Liaison aux protéines, Protéines de l'enveloppe virale, Pénétration virale, Souris.
English descriptors
- KwdEn :
- Animals, Carcinoembryonic Antigen (metabolism), Cathepsins (metabolism), Liposomes (metabolism), Membrane Glycoproteins (chemistry), Membrane Glycoproteins (genetics), Membrane Glycoproteins (metabolism), Mice, Murine hepatitis virus (metabolism), Protein Binding, Protein Conformation, Spike Glycoprotein, Coronavirus, Trypsin (metabolism), Viral Envelope Proteins (chemistry), Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism), Virus Internalization.
- MESH :
- chemical , chemistry : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Carcinoembryonic Antigen, Cathepsins, Liposomes, Membrane Glycoproteins, Trypsin, Viral Envelope Proteins.
- metabolism : Murine hepatitis virus.
- Animals, Mice, Protein Binding, Protein Conformation, Spike Glycoprotein, Coronavirus, Virus Internalization.
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.
DOI: 10.1128/JVI.00959-09
PubMed: 19706706
Affiliations:
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uniqKey="Taguchi F" first="Fumihiro" last="Taguchi">Fumihiro Taguchi</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Carcinoembryonic Antigen (metabolism)</term><term>Cathepsins (metabolism)</term><term>Liposomes (metabolism)</term><term>Membrane Glycoproteins (chemistry)</term><term>Membrane Glycoproteins (genetics)</term><term>Membrane Glycoproteins (metabolism)</term><term>Mice</term><term>Murine hepatitis virus (metabolism)</term><term>Protein Binding</term><term>Protein Conformation</term><term>Spike Glycoprotein, Coronavirus</term><term>Trypsin (metabolism)</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (metabolism)</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antigène carcinoembryonnaire (métabolisme)</term><term>Cathepsines (métabolisme)</term><term>Conformation des protéines</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (génétique)</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Liaison aux protéines</term><term>Liposomes (métabolisme)</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Pénétration virale</term><term>Souris</term><term>Trypsine (métabolisme)</term><term>Virus de l'hépatite murine (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Carcinoembryonic Antigen</term><term>Cathepsins</term><term>Liposomes</term><term>Membrane Glycoproteins</term><term>Trypsin</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Murine hepatitis virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigène carcinoembryonnaire</term><term>Cathepsines</term><term>Glycoprotéines membranaires</term><term>Liposomes</term><term>Protéines de l'enveloppe virale</term><term>Trypsine</term><term>Virus de l'hépatite murine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Mice</term><term>Protein Binding</term><term>Protein Conformation</term><term>Spike Glycoprotein, Coronavirus</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Conformation des protéines</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Liaison aux protéines</term><term>Protéines de l'enveloppe virale</term><term>Pénétration virale</term><term>Souris</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><noCountry><name sortKey="Taguchi, Fumihiro" sort="Taguchi, Fumihiro" uniqKey="Taguchi F" first="Fumihiro" last="Taguchi">Fumihiro Taguchi</name></noCountry><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></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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