The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal
Identifieur interne : 002303 ( Ncbi/Merge ); précédent : 002302; suivant : 002304The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal
Auteurs : Anabelle Perrier [France] ; Ariane Bonnin [France] ; Lowiese Desmarets [France] ; Adeline Danneels [France] ; Anne Goffard [France] ; Yves Rouillé [France] ; Jean Dubuisson [France] ; Sandrine Belouzard [France]Source :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2019.
Abstract
Coronavirus M proteins represent the major protein component of the viral
envelope. They play an essential role during viral assembly by interacting with
all of the other structural proteins. Coronaviruses bud into the endoplasmic
reticulum (ER)–Golgi intermediate compartment (ERGIC), but the mechanisms
by which M proteins are transported from their site of synthesis, the ER, to the
budding site remain poorly understood. Here, we investigated the intracellular
trafficking of the Middle East respiratory syndrome coronavirus (MERS-CoV) M
protein. Subcellular localization analyses revealed that the MERS-CoV M protein
is retained intracellularly in the
Url:
DOI: 10.1074/jbc.RA119.008964
PubMed: 31399512
PubMed Central: 6768645
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-Golgi network localization signal</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The C-terminal domain of the MERS coronavirus M protein contains a
<italic>trans</italic>
-Golgi network localization signal</title>
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<author><name sortKey="Goffard, Anne" sort="Goffard, Anne" uniqKey="Goffard A" first="Anne" last="Goffard">Anne Goffard</name>
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<country xml:lang="fr">France</country>
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<author><name sortKey="Rouille, Yves" sort="Rouille, Yves" uniqKey="Rouille Y" first="Yves" last="Rouillé">Yves Rouillé</name>
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<country xml:lang="fr">France</country>
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<placeName><region type="region" nuts="2">Hauts-de-France</region>
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<author><name sortKey="Dubuisson, Jean" sort="Dubuisson, Jean" uniqKey="Dubuisson J" first="Jean" last="Dubuisson">Jean Dubuisson</name>
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<country xml:lang="fr">France</country>
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<author><name sortKey="Belouzard, Sandrine" sort="Belouzard, Sandrine" uniqKey="Belouzard S" first="Sandrine" last="Belouzard">Sandrine Belouzard</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
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<series><title level="j">The Journal of Biological Chemistry</title>
<idno type="ISSN">0021-9258</idno>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2019">2019</date>
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<front><div type="abstract" xml:lang="en"><p>Coronavirus M proteins represent the major protein component of the viral
envelope. They play an essential role during viral assembly by interacting with
all of the other structural proteins. Coronaviruses bud into the endoplasmic
reticulum (ER)–Golgi intermediate compartment (ERGIC), but the mechanisms
by which M proteins are transported from their site of synthesis, the ER, to the
budding site remain poorly understood. Here, we investigated the intracellular
trafficking of the Middle East respiratory syndrome coronavirus (MERS-CoV) M
protein. Subcellular localization analyses revealed that the MERS-CoV M protein
is retained intracellularly in the <italic>trans</italic>
-Golgi network (TGN),
and we identified two motifs in the distal part of the C-terminal domain as
being important for this specific localization. We identified the first motif as
a functional diacidic DxE ER export signal, because substituting Asp-211 and
Glu-213 with alanine induced retention of the MERS-CoV M in the ER. The second
motif, <sup>199</sup>
KxGxYR<sup>204</sup>
, was responsible for retaining the M
protein in the TGN. Substitution of this motif resulted in MERS-CoV M leakage
toward the plasma membrane. We further confirmed the role of
<sup>199</sup>
KxGxYR<sup>204</sup>
as a TGN retention signal by using
chimeras between MERS-CoV M and the M protein of infectious bronchitis virus
(IBV). Our results indicated that the C-terminal domains of both proteins
determine their specific localization, namely TGN and
ERGIC/<italic>cis</italic>
-Golgi for MERS-M and IBV-M, respectively. Our
findings indicate that MERS-CoV M protein localizes to the TGN because of the
combined presence of an ER export signal and a TGN retention motif.</p>
</div>
</front>
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<double pmid="31399512"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The C-terminal domain of the MERS coronavirus M protein contains a
<italic>trans</italic>
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<author><name sortKey="Perrier, Anabelle" sort="Perrier, Anabelle" uniqKey="Perrier A" first="Anabelle" last="Perrier">Anabelle Perrier</name>
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<country xml:lang="fr">France</country>
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<author><name sortKey="Bonnin, Ariane" sort="Bonnin, Ariane" uniqKey="Bonnin A" first="Ariane" last="Bonnin">Ariane Bonnin</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
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<country xml:lang="fr">France</country>
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<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
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<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
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<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
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</author>
<author><name sortKey="Rouille, Yves" sort="Rouille, Yves" uniqKey="Rouille Y" first="Yves" last="Rouillé">Yves Rouillé</name>
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<country xml:lang="fr">France</country>
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</affiliation>
</author>
<author><name sortKey="Dubuisson, Jean" sort="Dubuisson, Jean" uniqKey="Dubuisson J" first="Jean" last="Dubuisson">Jean Dubuisson</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Belouzard, Sandrine" sort="Belouzard, Sandrine" uniqKey="Belouzard S" first="Sandrine" last="Belouzard">Sandrine Belouzard</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">31399512</idno>
<idno type="pmc">6768645</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768645</idno>
<idno type="RBID">PMC:6768645</idno>
<idno type="doi">10.1074/jbc.RA119.008964</idno>
<date when="2019">2019</date>
<idno type="wicri:Area/Pmc/Corpus">000D84</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D84</idno>
<idno type="wicri:Area/Pmc/Curation">000D84</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000D84</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000159</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000159</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The C-terminal domain of the MERS coronavirus M protein contains a
<italic>trans</italic>
-Golgi network localization signal</title>
<author><name sortKey="Perrier, Anabelle" sort="Perrier, Anabelle" uniqKey="Perrier A" first="Anabelle" last="Perrier">Anabelle Perrier</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bonnin, Ariane" sort="Bonnin, Ariane" uniqKey="Bonnin A" first="Ariane" last="Bonnin">Ariane Bonnin</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Desmarets, Lowiese" sort="Desmarets, Lowiese" uniqKey="Desmarets L" first="Lowiese" last="Desmarets">Lowiese Desmarets</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Danneels, Adeline" sort="Danneels, Adeline" uniqKey="Danneels A" first="Adeline" last="Danneels">Adeline Danneels</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Goffard, Anne" sort="Goffard, Anne" uniqKey="Goffard A" first="Anne" last="Goffard">Anne Goffard</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rouille, Yves" sort="Rouille, Yves" uniqKey="Rouille Y" first="Yves" last="Rouillé">Yves Rouillé</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dubuisson, Jean" sort="Dubuisson, Jean" uniqKey="Dubuisson J" first="Jean" last="Dubuisson">Jean Dubuisson</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Belouzard, Sandrine" sort="Belouzard, Sandrine" uniqKey="Belouzard S" first="Sandrine" last="Belouzard">Sandrine Belouzard</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of Biological Chemistry</title>
<idno type="ISSN">0021-9258</idno>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Coronavirus M proteins represent the major protein component of the viral
envelope. They play an essential role during viral assembly by interacting with
all of the other structural proteins. Coronaviruses bud into the endoplasmic
reticulum (ER)–Golgi intermediate compartment (ERGIC), but the mechanisms
by which M proteins are transported from their site of synthesis, the ER, to the
budding site remain poorly understood. Here, we investigated the intracellular
trafficking of the Middle East respiratory syndrome coronavirus (MERS-CoV) M
protein. Subcellular localization analyses revealed that the MERS-CoV M protein
is retained intracellularly in the <italic>trans</italic>
-Golgi network (TGN),
and we identified two motifs in the distal part of the C-terminal domain as
being important for this specific localization. We identified the first motif as
a functional diacidic DxE ER export signal, because substituting Asp-211 and
Glu-213 with alanine induced retention of the MERS-CoV M in the ER. The second
motif, <sup>199</sup>
KxGxYR<sup>204</sup>
, was responsible for retaining the M
protein in the TGN. Substitution of this motif resulted in MERS-CoV M leakage
toward the plasma membrane. We further confirmed the role of
<sup>199</sup>
KxGxYR<sup>204</sup>
as a TGN retention signal by using
chimeras between MERS-CoV M and the M protein of infectious bronchitis virus
(IBV). Our results indicated that the C-terminal domains of both proteins
determine their specific localization, namely TGN and
ERGIC/<italic>cis</italic>
-Golgi for MERS-M and IBV-M, respectively. Our
findings indicate that MERS-CoV M protein localizes to the TGN because of the
combined presence of an ER export signal and a TGN retention motif.</p>
</div>
</front>
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S. Masters</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name>
</author>
<author><name sortKey="Netland, J" uniqKey="Netland J">J. Netland</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Corman, V X0a M" uniqKey="Corman V">V.
M. Corman</name>
</author>
<author><name sortKey="Muth, D" uniqKey="Muth D">D. Muth</name>
</author>
<author><name sortKey="Niemeyer, D" uniqKey="Niemeyer D">D. Niemeyer</name>
</author>
<author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Belouzard, S" uniqKey="Belouzard S">S. Belouzard</name>
</author>
<author><name sortKey="Millet, J X0a K" uniqKey="Millet J">J.
K. Millet</name>
</author>
<author><name sortKey="Licitra, B X0a N" uniqKey="Licitra B">B.
N. Licitra</name>
</author>
<author><name sortKey="Whittaker, G X0a R" uniqKey="Whittaker G">G.
R. Whittaker</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Heald Sargent, T" uniqKey="Heald Sargent T">T. Heald-Sargent</name>
</author>
<author><name sortKey="Gallagher, T" uniqKey="Gallagher T">T. Gallagher</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ruch, T X0a R" uniqKey="Ruch T">T.
R. Ruch</name>
</author>
<author><name sortKey="Machamer, C X0a E" uniqKey="Machamer C">C.
E. Machamer</name>
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</analytic>
</biblStruct>
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L. Nieto-Torres</name>
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<author><name sortKey="Verdia Baguena, C" uniqKey="Verdia Baguena C">C. Verdiá-Báguena</name>
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<author><name sortKey="Casta O Rodriguez, C" uniqKey="Casta O Rodriguez C">C. Castaño-Rodriguez</name>
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M. Aguilella</name>
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<author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L. Enjuanes</name>
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<biblStruct><analytic><author><name sortKey="Tseng, Y T" uniqKey="Tseng Y">Y.-T. Tseng</name>
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<biblStruct><analytic><author><name sortKey="Baudoux, P" uniqKey="Baudoux P">P. Baudoux</name>
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-Golgi network localization signal.</title>
<author><name sortKey="Perrier, Anabelle" sort="Perrier, Anabelle" uniqKey="Perrier A" first="Anabelle" last="Perrier">Anabelle Perrier</name>
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<affiliation wicri:level="3"><nlm:affiliation>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dubuisson, Jean" sort="Dubuisson, Jean" uniqKey="Dubuisson J" first="Jean" last="Dubuisson">Jean Dubuisson</name>
<affiliation wicri:level="3"><nlm:affiliation>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Belouzard, Sandrine" sort="Belouzard, Sandrine" uniqKey="Belouzard S" first="Sandrine" last="Belouzard">Sandrine Belouzard</name>
<affiliation wicri:level="3"><nlm:affiliation>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France sandrine.belouzard@ibl.cnrs.fr.</nlm:affiliation>
<country wicri:rule="url">France</country>
<wicri:regionArea>Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of biological chemistry</title>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2019" type="published">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Coronavirus M proteins represent the major protein component of the viral envelope. They play an essential role during viral assembly by interacting with all of the other structural proteins. Coronaviruses bud into the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), but the mechanisms by which M proteins are transported from their site of synthesis, the ER, to the budding site remain poorly understood. Here, we investigated the intracellular trafficking of the Middle East respiratory syndrome coronavirus (MERS-CoV) M protein. Subcellular localization analyses revealed that the MERS-CoV M protein is retained intracellularly in the <i>trans</i>
-Golgi network (TGN), and we identified two motifs in the distal part of the C-terminal domain as being important for this specific localization. We identified the first motif as a functional diacidic DxE ER export signal, because substituting Asp-211 and Glu-213 with alanine induced retention of the MERS-CoV M in the ER. The second motif, <sup>199</sup>
KxGxYR<sup>204</sup>
, was responsible for retaining the M protein in the TGN. Substitution of this motif resulted in MERS-CoV M leakage toward the plasma membrane. We further confirmed the role of <sup>199</sup>
KxGxYR<sup>204</sup>
as a TGN retention signal by using chimeras between MERS-CoV M and the M protein of infectious bronchitis virus (IBV). Our results indicated that the C-terminal domains of both proteins determine their specific localization, namely TGN and ERGIC/<i>cis</i>
-Golgi for MERS-M and IBV-M, respectively. Our findings indicate that MERS-CoV M protein localizes to the TGN because of the combined presence of an ER export signal and a TGN retention motif.</div>
</front>
</TEI>
</pubmed>
</double>
</record>
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