Dynamic Motion and Communication in the Streptococcal C1 Phage Lysin, PlyC
Identifieur interne : 002E95 ( Main/Exploration ); précédent : 002E94; suivant : 002E96Dynamic Motion and Communication in the Streptococcal C1 Phage Lysin, PlyC
Auteurs : Blake T. Riley [Australie] ; Sebastian S. Broendum [Australie] ; Cyril F. Reboul [Australie] ; Nathan P. Cowieson [Australie] ; Mauricio G. S. Costa [Brésil] ; Itamar Kass [Australie] ; Colin Jackson [Australie] ; David Perahia [France] ; Ashley M. Buckle [Australie] ; Sheena Mcgowan [Australie]Source :
- PLoS ONE [ 1932-6203 ] ; 2015.
Descripteurs français
- KwdFr :
- Bactériophages (), Bactériophages (enzymologie), Cristallographie aux rayons X (), Diffusion aux petits angles, Domaine catalytique, Enzymes (), Enzymes (métabolisme), Modèles moléculaires, Simulation de dynamique moléculaire, Streptococcus (virologie), Structure quaternaire des protéines, Structure secondaire des protéines.
- MESH :
- enzymologie : Bactériophages.
- métabolisme : Enzymes.
- virologie : Streptococcus.
- Bactériophages, Cristallographie aux rayons X, Diffusion aux petits angles, Domaine catalytique, Enzymes, Modèles moléculaires, Simulation de dynamique moléculaire, Structure quaternaire des protéines, Structure secondaire des protéines.
English descriptors
- KwdEn :
- Bacteriophages (chemistry), Bacteriophages (enzymology), Catalytic Domain, Crystallography, X-Ray (methods), Enzymes (chemistry), Enzymes (metabolism), Models, Molecular, Molecular Dynamics Simulation, Protein Structure, Quaternary, Protein Structure, Secondary, Scattering, Small Angle, Streptococcus (virology).
- MESH :
- chemical , chemistry : Enzymes.
- chemistry : Bacteriophages.
- enzymology : Bacteriophages.
- chemical , metabolism : Enzymes.
- methods : Crystallography, X-Ray.
- virology : Streptococcus.
- Catalytic Domain, Models, Molecular, Molecular Dynamics Simulation, Protein Structure, Quaternary, Protein Structure, Secondary, Scattering, Small Angle.
Abstract
The growing problem of antibiotic resistance underlies the critical need to develop new treatments to prevent and control resistant bacterial infection. Exogenous application of bacteriophage lysins results in rapid and specific destruction of Gram-positive bacteria and therefore lysins represent novel antibacterial agents. The PlyC phage lysin is the most potent lysin characterized to date and can rapidly lyse Group A, C and E streptococci. Previously, we have determined the X-ray crystal structure of PlyC, revealing a complicated and unique arrangement of nine proteins. The scaffold features a multimeric cell-wall docking assembly bound to two catalytic domains that communicate and work synergistically. However, the crystal structure appeared to be auto-inhibited and raised important questions as to the mechanism underlying its extreme potency. Here we use small angle X-ray scattering (SAXS) and reveal that the conformational ensemble of PlyC in solution is different to that in the crystal structure. We also investigated the flexibility of the enzyme using both normal mode (NM) analysis and molecular dynamics (MD) simulations. Consistent with our SAXS data, MD simulations show rotational dynamics of both catalytic domains, and implicate inter-domain communication in achieving a substrate-ready conformation required for enzyme function. Our studies therefore provide insights into how the domains in the PlyC holoenzyme may act together to achieve its extraordinary potency.
Url:
DOI: 10.1371/journal.pone.0140219
PubMed: 26470022
PubMed Central: 4607406
Affiliations:
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Le document en format XML
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Cowieson</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Australian Synchrotron, Clayton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Synchrotron, Clayton</wicri:regionArea><wicri:noRegion>Clayton</wicri:noRegion></affiliation></author><author><name sortKey="Costa, Mauricio G S" sort="Costa, Mauricio G S" uniqKey="Costa M" first="Mauricio G. S." last="Costa">Mauricio G. S. Costa</name><affiliation wicri:level="3"><nlm:aff id="aff004"><addr-line>Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil</addr-line></nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro</wicri:regionArea><placeName><settlement type="city">Rio de Janeiro</settlement><region type="state">État de Rio de Janeiro</region></placeName></affiliation></author><author><name sortKey="Kass, Itamar" sort="Kass, Itamar" uniqKey="Kass I" first="Itamar" last="Kass">Itamar Kass</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton</wicri:regionArea><wicri:noRegion>Clayton</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Victorian Life Sciences Computation Initiative Life Sciences Computation Centre, Monash University, Clayton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Victorian Life Sciences Computation Initiative Life Sciences Computation Centre, Monash University, Clayton</wicri:regionArea><wicri:noRegion>Clayton</wicri:noRegion></affiliation></author><author><name sortKey="Jackson, Colin" sort="Jackson, Colin" uniqKey="Jackson C" first="Colin" last="Jackson">Colin Jackson</name><affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Research School of Chemistry, Australian National University, Canberra, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Research School of Chemistry, Australian National University, Canberra</wicri:regionArea><wicri:noRegion>Canberra</wicri:noRegion></affiliation></author><author><name sortKey="Perahia, David" sort="Perahia, David" uniqKey="Perahia D" first="David" last="Perahia">David Perahia</name><affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>Laboratoire de Biologie et de Pharmacologie Appliquée, Ecole Normale Supérieure de Cachan, Centre National de la Recherche Scientifique, Cachan, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biologie et de Pharmacologie Appliquée, Ecole Normale Supérieure de Cachan, Centre National de la Recherche Scientifique, Cachan</wicri:regionArea><wicri:noRegion>Cachan</wicri:noRegion><wicri:noRegion>Cachan</wicri:noRegion></affiliation></author><author><name sortKey="Buckle, Ashley M" sort="Buckle, Ashley M" uniqKey="Buckle A" first="Ashley M." last="Buckle">Ashley M. Buckle</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton</wicri:regionArea><wicri:noRegion>Clayton</wicri:noRegion></affiliation></author><author><name sortKey="Mcgowan, Sheena" sort="Mcgowan, Sheena" uniqKey="Mcgowan S" first="Sheena" last="Mcgowan">Sheena Mcgowan</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton</wicri:regionArea><wicri:noRegion>Clayton</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton</wicri:regionArea><wicri:noRegion>Clayton</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Bacteriophages (chemistry)</term><term>Bacteriophages (enzymology)</term><term>Catalytic Domain</term><term>Crystallography, X-Ray (methods)</term><term>Enzymes (chemistry)</term><term>Enzymes (metabolism)</term><term>Models, Molecular</term><term>Molecular Dynamics Simulation</term><term>Protein Structure, Quaternary</term><term>Protein Structure, Secondary</term><term>Scattering, Small Angle</term><term>Streptococcus (virology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Bactériophages ()</term><term>Bactériophages (enzymologie)</term><term>Cristallographie aux rayons X ()</term><term>Diffusion aux petits angles</term><term>Domaine catalytique</term><term>Enzymes ()</term><term>Enzymes (métabolisme)</term><term>Modèles moléculaires</term><term>Simulation de dynamique moléculaire</term><term>Streptococcus (virologie)</term><term>Structure quaternaire des protéines</term><term>Structure secondaire des protéines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Enzymes</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Bacteriophages</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Bactériophages</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Bacteriophages</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Enzymes</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Crystallography, X-Ray</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Enzymes</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Streptococcus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Streptococcus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Catalytic Domain</term><term>Models, Molecular</term><term>Molecular Dynamics Simulation</term><term>Protein Structure, Quaternary</term><term>Protein Structure, Secondary</term><term>Scattering, Small Angle</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Bactériophages</term><term>Cristallographie aux rayons X</term><term>Diffusion aux petits angles</term><term>Domaine catalytique</term><term>Enzymes</term><term>Modèles moléculaires</term><term>Simulation de dynamique moléculaire</term><term>Structure quaternaire des protéines</term><term>Structure secondaire des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The growing problem of antibiotic resistance underlies the critical need to develop new treatments to prevent and control resistant bacterial infection. Exogenous application of bacteriophage lysins results in rapid and specific destruction of Gram-positive bacteria and therefore lysins represent novel antibacterial agents. The PlyC phage lysin is the most potent lysin characterized to date and can rapidly lyse Group A, C and E streptococci. Previously, we have determined the X-ray crystal structure of PlyC, revealing a complicated and unique arrangement of nine proteins. The scaffold features a multimeric cell-wall docking assembly bound to two catalytic domains that communicate and work synergistically. However, the crystal structure appeared to be auto-inhibited and raised important questions as to the mechanism underlying its extreme potency. Here we use small angle X-ray scattering (SAXS) and reveal that the conformational ensemble of PlyC in solution is different to that in the crystal structure. We also investigated the flexibility of the enzyme using both normal mode (NM) analysis and molecular dynamics (MD) simulations. Consistent with our SAXS data, MD simulations show rotational dynamics of both catalytic domains, and implicate inter-domain communication in achieving a substrate-ready conformation required for enzyme function. Our studies therefore provide insights into how the domains in the PlyC holoenzyme may act together to achieve its extraordinary potency.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Gravitz, L" uniqKey="Gravitz L">L Gravitz</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Matsuzaki, S" uniqKey="Matsuzaki S">S Matsuzaki</name></author><author><name sortKey="Rashel, M" uniqKey="Rashel M">M Rashel</name></author><author><name sortKey="Uchiyama, J" uniqKey="Uchiyama J">J Uchiyama</name></author><author><name sortKey="Sakurai, S" uniqKey="Sakurai S">S Sakurai</name></author><author><name sortKey="Ujihara, T" uniqKey="Ujihara T">T Ujihara</name></author><author><name sortKey="Kuroda, M" uniqKey="Kuroda M">M Kuroda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loessner, Mj" uniqKey="Loessner M">MJ 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Pedro</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>Brésil</li><li>France</li></country><region><li>État de Rio de Janeiro</li></region><settlement><li>Rio de Janeiro</li></settlement></list><tree><country name="Australie"><noRegion><name sortKey="Riley, Blake T" sort="Riley, Blake T" uniqKey="Riley B" first="Blake T." last="Riley">Blake T. Riley</name></noRegion><name sortKey="Broendum, Sebastian S" sort="Broendum, Sebastian S" uniqKey="Broendum S" first="Sebastian S." last="Broendum">Sebastian S. Broendum</name><name sortKey="Buckle, Ashley M" sort="Buckle, Ashley M" uniqKey="Buckle A" first="Ashley M." last="Buckle">Ashley M. Buckle</name><name sortKey="Cowieson, Nathan P" sort="Cowieson, Nathan P" uniqKey="Cowieson N" first="Nathan P." last="Cowieson">Nathan P. Cowieson</name><name sortKey="Jackson, Colin" sort="Jackson, Colin" uniqKey="Jackson C" first="Colin" last="Jackson">Colin Jackson</name><name sortKey="Kass, Itamar" sort="Kass, Itamar" uniqKey="Kass I" first="Itamar" last="Kass">Itamar Kass</name><name sortKey="Kass, Itamar" sort="Kass, Itamar" uniqKey="Kass I" first="Itamar" last="Kass">Itamar Kass</name><name sortKey="Mcgowan, Sheena" sort="Mcgowan, Sheena" uniqKey="Mcgowan S" first="Sheena" last="Mcgowan">Sheena Mcgowan</name><name sortKey="Mcgowan, Sheena" sort="Mcgowan, Sheena" uniqKey="Mcgowan S" first="Sheena" last="Mcgowan">Sheena Mcgowan</name><name sortKey="Reboul, Cyril F" sort="Reboul, Cyril F" uniqKey="Reboul C" first="Cyril F." last="Reboul">Cyril F. Reboul</name><name sortKey="Reboul, Cyril F" sort="Reboul, Cyril F" uniqKey="Reboul C" first="Cyril F." last="Reboul">Cyril F. Reboul</name></country><country name="Brésil"><region name="État de Rio de Janeiro"><name sortKey="Costa, Mauricio G S" sort="Costa, Mauricio G S" uniqKey="Costa M" first="Mauricio G. S." last="Costa">Mauricio G. S. Costa</name></region></country><country name="France"><noRegion><name sortKey="Perahia, David" sort="Perahia, David" uniqKey="Perahia D" first="David" last="Perahia">David Perahia</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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