Conductance and amantadine binding of a pore formed by a lysine-flanked transmembrane domain of SARS coronavirus envelope protein.
Identifieur interne : 003744 ( Main/Exploration ); précédent : 003743; suivant : 003745Conductance and amantadine binding of a pore formed by a lysine-flanked transmembrane domain of SARS coronavirus envelope protein.
Auteurs : Jaume Torres [Singapour] ; Uma Maheswari ; Krupakar Parthasarathy ; Lifang Ng ; Ding Xiang Liu ; Xiandi GongSource :
- Protein science : a publication of the Protein Society [ 0961-8368 ] ; 2007.
Descripteurs français
- KwdFr :
- Amantadine (métabolisme), Amantadine (pharmacologie), Antiviraux (métabolisme), Antiviraux (pharmacologie), Conductivité électrique, Double couche lipidique (), Lysine (), Modèles moléculaires, Mutation, Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (métabolisme), Relation dose-effet des médicaments, Relation structure-activité, Résonance plasmonique de surface, Structure tertiaire des protéines, Virus du SRAS (métabolisme).
- MESH :
- génétique : Protéines de l'enveloppe virale.
- métabolisme : Amantadine, Antiviraux, Protéines de l'enveloppe virale, Virus du SRAS.
- pharmacologie : Amantadine, Antiviraux.
- Conductivité électrique, Double couche lipidique, Lysine, Modèles moléculaires, Mutation, Protéines de l'enveloppe virale, Relation dose-effet des médicaments, Relation structure-activité, Résonance plasmonique de surface, Structure tertiaire des protéines.
English descriptors
- KwdEn :
- Amantadine (metabolism), Amantadine (pharmacology), Antiviral Agents (metabolism), Antiviral Agents (pharmacology), Dose-Response Relationship, Drug, Electric Conductivity, Lipid Bilayers (chemistry), Lysine (chemistry), Models, Molecular, Mutation, Protein Structure, Tertiary, SARS Virus (metabolism), Structure-Activity Relationship, Surface Plasmon Resonance, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , chemistry : Lipid Bilayers, Lysine, Viral Envelope Proteins.
- chemical , genetics : Viral Envelope Proteins.
- chemical , metabolism : Amantadine, Antiviral Agents, Viral Envelope Proteins.
- chemical , pharmacology : Amantadine, Antiviral Agents.
- metabolism : SARS Virus.
- Dose-Response Relationship, Drug, Electric Conductivity, Models, Molecular, Mutation, Protein Structure, Tertiary, Structure-Activity Relationship, Surface Plasmon Resonance.
Abstract
The coronavirus responsible for the severe acute respiratory syndrome (SARS-CoV) contains a small envelope protein, E, with putative involvement in host cell apoptosis and virus morphogenesis. It has been suggested that E protein can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a regular TM alpha-helical bundle. We have shown previously that the topology of the alpha-helical putative TM domain of E protein (ETM), flanked by two lysine residues at C and N termini to improve solubility, is consistent with a regular TM alpha-helix, with orientational parameters in lipid bilayers that are consistent with a homopentameric model. Herein, we show that this peptide, reconstituted in lipid bilayers, shows sodium conductance. Channel activity is inhibited by the anti-influenza drug amantadine, which was found to bind our preparation with moderate affinity. Results obtained from single or double mutants indicate that the organization of the transmembrane pore is consistent with our previously reported pentameric alpha-helical bundle model.
DOI: 10.1110/ps.062730007
PubMed: 17766393
Affiliations:
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Le document en format XML
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<author><name sortKey="Gong, Xiandi" sort="Gong, Xiandi" uniqKey="Gong X" first="Xiandi" last="Gong">Xiandi Gong</name>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amantadine (metabolism)</term>
<term>Amantadine (pharmacology)</term>
<term>Antiviral Agents (metabolism)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Electric Conductivity</term>
<term>Lipid Bilayers (chemistry)</term>
<term>Lysine (chemistry)</term>
<term>Models, Molecular</term>
<term>Mutation</term>
<term>Protein Structure, Tertiary</term>
<term>SARS Virus (metabolism)</term>
<term>Structure-Activity Relationship</term>
<term>Surface Plasmon Resonance</term>
<term>Viral Envelope Proteins (chemistry)</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Amantadine (métabolisme)</term>
<term>Amantadine (pharmacologie)</term>
<term>Antiviraux (métabolisme)</term>
<term>Antiviraux (pharmacologie)</term>
<term>Conductivité électrique</term>
<term>Double couche lipidique ()</term>
<term>Lysine ()</term>
<term>Modèles moléculaires</term>
<term>Mutation</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>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Résonance plasmonique de surface</term>
<term>Structure tertiaire des protéines</term>
<term>Virus du SRAS (métabolisme)</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Lipid Bilayers</term>
<term>Lysine</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Amantadine</term>
<term>Antiviral Agents</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Amantadine</term>
<term>Antiviral Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines de l'enveloppe virale</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term>
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<term>Antiviraux</term>
<term>Protéines de l'enveloppe virale</term>
<term>Virus du SRAS</term>
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<term>Antiviraux</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Dose-Response Relationship, Drug</term>
<term>Electric Conductivity</term>
<term>Models, Molecular</term>
<term>Mutation</term>
<term>Protein Structure, Tertiary</term>
<term>Structure-Activity Relationship</term>
<term>Surface Plasmon Resonance</term>
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<term>Double couche lipidique</term>
<term>Lysine</term>
<term>Modèles moléculaires</term>
<term>Mutation</term>
<term>Protéines de l'enveloppe virale</term>
<term>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Résonance plasmonique de surface</term>
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<front><div type="abstract" xml:lang="en">The coronavirus responsible for the severe acute respiratory syndrome (SARS-CoV) contains a small envelope protein, E, with putative involvement in host cell apoptosis and virus morphogenesis. It has been suggested that E protein can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a regular TM alpha-helical bundle. We have shown previously that the topology of the alpha-helical putative TM domain of E protein (ETM), flanked by two lysine residues at C and N termini to improve solubility, is consistent with a regular TM alpha-helix, with orientational parameters in lipid bilayers that are consistent with a homopentameric model. Herein, we show that this peptide, reconstituted in lipid bilayers, shows sodium conductance. Channel activity is inhibited by the anti-influenza drug amantadine, which was found to bind our preparation with moderate affinity. Results obtained from single or double mutants indicate that the organization of the transmembrane pore is consistent with our previously reported pentameric alpha-helical bundle model.</div>
</front>
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<name sortKey="Liu, Ding Xiang" sort="Liu, Ding Xiang" uniqKey="Liu D" first="Ding Xiang" last="Liu">Ding Xiang Liu</name>
<name sortKey="Maheswari, Uma" sort="Maheswari, Uma" uniqKey="Maheswari U" first="Uma" last="Maheswari">Uma Maheswari</name>
<name sortKey="Ng, Lifang" sort="Ng, Lifang" uniqKey="Ng L" first="Lifang" last="Ng">Lifang Ng</name>
<name sortKey="Parthasarathy, Krupakar" sort="Parthasarathy, Krupakar" uniqKey="Parthasarathy K" first="Krupakar" last="Parthasarathy">Krupakar Parthasarathy</name>
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<country name="Singapour"><noRegion><name sortKey="Torres, Jaume" sort="Torres, Jaume" uniqKey="Torres J" first="Jaume" last="Torres">Jaume Torres</name>
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