Structural basis for the dimerization and substrate recognition specificity of porcine epidemic diarrhea virus 3C-like protease
Identifieur interne : 002C50 ( Ncbi/Checkpoint ); précédent : 002C49; suivant : 002C51Structural basis for the dimerization and substrate recognition specificity of porcine epidemic diarrhea virus 3C-like protease
Auteurs : Gang Ye [République populaire de Chine] ; Feng Deng [République populaire de Chine] ; Zhou Shen [République populaire de Chine] ; Rui Luo [République populaire de Chine] ; Ling Zhao [République populaire de Chine] ; Shaobo Xiao [République populaire de Chine] ; Zhen F. Fu [République populaire de Chine, États-Unis] ; Guiqing Peng [République populaire de Chine]Source :
- Virology [ 0042-6822 ] ; 2016.
Descripteurs français
- KwdFr :
- Activation enzymatique, Animaux, Catalyse, Conformation des protéines, Domaine catalytique, Liaison aux protéines, Modèles moléculaires, Motifs d'acides aminés, Motifs et domaines d'intéraction protéique, Multimérisation de protéines, Peptide hydrolases (), Peptide hydrolases (métabolisme), Protéines virales (), Protéines virales (métabolisme), Relation structure-activité, Sites de fixation, Spécificité du substrat, Suidae, Séquence d'acides aminés, Virus de la diarrhée porcine épidémique (enzymologie).
- MESH :
- enzymologie : Virus de la diarrhée porcine épidémique.
- métabolisme : Peptide hydrolases, Protéines virales.
- Activation enzymatique, Animaux, Catalyse, Conformation des protéines, Domaine catalytique, Liaison aux protéines, Modèles moléculaires, Motifs d'acides aminés, Motifs et domaines d'intéraction protéique, Multimérisation de protéines, Peptide hydrolases, Protéines virales, Relation structure-activité, Sites de fixation, Spécificité du substrat, Suidae, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Catalysis, Catalytic Domain, Enzyme Activation, Models, Molecular, Peptide Hydrolases (chemistry), Peptide Hydrolases (metabolism), Porcine epidemic diarrhea virus (enzymology), Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Protein Multimerization, Structure-Activity Relationship, Substrate Specificity, Swine, Viral Proteins (chemistry), Viral Proteins (metabolism).
- MESH :
- chemical , chemistry : Peptide Hydrolases, Viral Proteins.
- chemical , metabolism : Peptide Hydrolases, Viral Proteins.
- enzymology : Porcine epidemic diarrhea virus.
- Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Catalysis, Catalytic Domain, Enzyme Activation, Models, Molecular, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Protein Multimerization, Structure-Activity Relationship, Substrate Specificity, Swine.
Abstract
Porcine epidemic diarrhea virus (PEDV), a member of the genus
Url:
DOI: 10.1016/j.virol.2016.04.018
PubMed: 27128350
PubMed Central: 7111274
Affiliations:
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sortKey="Zhao, Ling" sort="Zhao, Ling" uniqKey="Zhao L" first="Ling" last="Zhao">Ling Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff0005">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0010">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Xiao, Shaobo" sort="Xiao, Shaobo" uniqKey="Xiao S" first="Shaobo" 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xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Deng, Feng" sort="Deng, Feng" uniqKey="Deng F" first="Feng" last="Deng">Feng Deng</name><affiliation wicri:level="1"><nlm:aff id="aff0005">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0010">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Shen, Zhou" sort="Shen, Zhou" uniqKey="Shen Z" first="Zhou" last="Shen">Zhou Shen</name><affiliation wicri:level="1"><nlm:aff id="aff0005">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0010">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Luo, Rui" sort="Luo, Rui" uniqKey="Luo R" first="Rui" last="Luo">Rui Luo</name><affiliation wicri:level="1"><nlm:aff id="aff0005">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0010">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Ling" sort="Zhao, Ling" uniqKey="Zhao L" first="Ling" last="Zhao">Ling Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff0005">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0010">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Xiao, Shaobo" sort="Xiao, Shaobo" uniqKey="Xiao S" first="Shaobo" last="Xiao">Shaobo Xiao</name><affiliation wicri:level="1"><nlm:aff id="aff0005">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0010">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Fu, Zhen F" sort="Fu, Zhen F" uniqKey="Fu Z" first="Zhen F." last="Fu">Zhen F. Fu</name><affiliation wicri:level="1"><nlm:aff id="aff0005">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0010">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="aff0015">Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name><affiliation wicri:level="1"><nlm:aff id="aff0005">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0010">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0020">The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author></analytic><series><title level="j">Virology</title><idno type="ISSN">0042-6822</idno><idno type="eISSN">1096-0341</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Sequence</term><term>Animals</term><term>Binding Sites</term><term>Catalysis</term><term>Catalytic Domain</term><term>Enzyme Activation</term><term>Models, Molecular</term><term>Peptide Hydrolases (chemistry)</term><term>Peptide Hydrolases (metabolism)</term><term>Porcine epidemic diarrhea virus (enzymology)</term><term>Protein Binding</term><term>Protein Conformation</term><term>Protein Interaction Domains and Motifs</term><term>Protein Multimerization</term><term>Structure-Activity Relationship</term><term>Substrate Specificity</term><term>Swine</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation enzymatique</term><term>Animaux</term><term>Catalyse</term><term>Conformation des protéines</term><term>Domaine catalytique</term><term>Liaison aux protéines</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Motifs et domaines d'intéraction protéique</term><term>Multimérisation de protéines</term><term>Peptide hydrolases ()</term><term>Peptide hydrolases (métabolisme)</term><term>Protéines virales ()</term><term>Protéines virales (métabolisme)</term><term>Relation structure-activité</term><term>Sites de fixation</term><term>Spécificité du substrat</term><term>Suidae</term><term>Séquence d'acides aminés</term><term>Virus de la diarrhée porcine épidémique (enzymologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Peptide Hydrolases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Peptide Hydrolases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus de la diarrhée porcine épidémique</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Porcine epidemic diarrhea virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Peptide hydrolases</term><term>Protéines virales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Sequence</term><term>Animals</term><term>Binding Sites</term><term>Catalysis</term><term>Catalytic Domain</term><term>Enzyme Activation</term><term>Models, Molecular</term><term>Protein Binding</term><term>Protein Conformation</term><term>Protein Interaction Domains and Motifs</term><term>Protein Multimerization</term><term>Structure-Activity Relationship</term><term>Substrate Specificity</term><term>Swine</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation enzymatique</term><term>Animaux</term><term>Catalyse</term><term>Conformation des protéines</term><term>Domaine catalytique</term><term>Liaison aux protéines</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Motifs et domaines d'intéraction protéique</term><term>Multimérisation de protéines</term><term>Peptide hydrolases</term><term>Protéines virales</term><term>Relation structure-activité</term><term>Sites de fixation</term><term>Spécificité du substrat</term><term>Suidae</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Porcine epidemic diarrhea virus (PEDV), a member of the genus <italic>Alphacoronavirus</italic>, has caused significant damage to the Asian and American pork industries. Coronavirus 3C-like protease (3CL<sup>pro</sup>), which is involved in the processing of viral polyproteins for viral replication, is an appealing antiviral drug target. Here, we present the crystal structures of PEDV 3CL<sup>pro</sup> and a molecular complex between an inactive PEDV 3CL<sup>pro</sup> variant C144A bound to a peptide substrate. Structural characterization, mutagenesis and biochemical analysis reveal the substrate-binding pockets and the residues that comprise the active site of PEDV 3CL<sup>pro</sup>. The dimerization of PEDV 3CL<sup>pro</sup> is similar to that of other <italic>Alphacoronavirus</italic> 3CL<sup>pro</sup>s but has several differences from that of SARS-CoV 3CL<sup>pro</sup> from the genus <italic>Betacoronavirus</italic>. Furthermore, the non-conserved motifs in the pockets cause different cleavage of substrate between PEDV and SARS-CoV 3CL<sup>pro</sup>s, which may provide new insights into the recognition of substrates by 3CL<sup>pro</sup>s in various coronavirus genera.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Adams, M J" uniqKey="Adams M">M.J. Adams</name></author><author><name sortKey="Carstens, E B" uniqKey="Carstens E">E.B. Carstens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adams, P D" uniqKey="Adams P">P.D. Adams</name></author><author><name sortKey="Grosse Kunstleve, R W" uniqKey="Grosse Kunstleve R">R.W. Grosse-Kunstleve</name></author><author><name sortKey="Hung, L W" uniqKey="Hung L">L.W. Hung</name></author><author><name sortKey="Ioerger, T R" uniqKey="Ioerger T">T.R. Ioerger</name></author><author><name sortKey="Mccoy, A J" uniqKey="Mccoy A">A.J. 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Snijder</name></author><author><name sortKey="Gorbalenya, A E" uniqKey="Gorbalenya A">A.E. Gorbalenya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Siddell, S G" uniqKey="Siddell S">S.G. Siddell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Géorgie (États-Unis)</li></region></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Ye, Gang" sort="Ye, Gang" uniqKey="Ye G" first="Gang" last="Ye">Gang Ye</name></noRegion><name sortKey="Deng, Feng" sort="Deng, Feng" uniqKey="Deng F" first="Feng" last="Deng">Feng Deng</name><name sortKey="Deng, Feng" sort="Deng, Feng" uniqKey="Deng F" first="Feng" last="Deng">Feng Deng</name><name sortKey="Fu, Zhen F" sort="Fu, Zhen F" uniqKey="Fu Z" first="Zhen F." last="Fu">Zhen F. Fu</name><name sortKey="Fu, Zhen F" sort="Fu, Zhen F" uniqKey="Fu Z" first="Zhen F." last="Fu">Zhen F. Fu</name><name sortKey="Luo, Rui" sort="Luo, Rui" uniqKey="Luo R" first="Rui" last="Luo">Rui Luo</name><name sortKey="Luo, Rui" sort="Luo, Rui" uniqKey="Luo R" first="Rui" last="Luo">Rui Luo</name><name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name><name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name><name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name><name sortKey="Shen, Zhou" sort="Shen, Zhou" uniqKey="Shen Z" first="Zhou" last="Shen">Zhou Shen</name><name sortKey="Shen, Zhou" sort="Shen, Zhou" uniqKey="Shen Z" first="Zhou" last="Shen">Zhou Shen</name><name sortKey="Xiao, Shaobo" sort="Xiao, Shaobo" uniqKey="Xiao S" first="Shaobo" last="Xiao">Shaobo Xiao</name><name sortKey="Xiao, Shaobo" sort="Xiao, Shaobo" uniqKey="Xiao S" first="Shaobo" last="Xiao">Shaobo Xiao</name><name sortKey="Ye, Gang" sort="Ye, Gang" uniqKey="Ye G" first="Gang" last="Ye">Gang Ye</name><name sortKey="Zhao, Ling" sort="Zhao, Ling" uniqKey="Zhao L" first="Ling" last="Zhao">Ling Zhao</name><name sortKey="Zhao, Ling" sort="Zhao, Ling" uniqKey="Zhao L" first="Ling" last="Zhao">Ling Zhao</name></country><country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="Fu, Zhen F" sort="Fu, Zhen F" uniqKey="Fu Z" first="Zhen F." last="Fu">Zhen F. 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