The Molecular Mechanisms Underlying the Hijack of Host Proteins by the 1918 Spanish Influenza Virus.
Identifieur interne : 000643 ( Main/Exploration ); précédent : 000642; suivant : 000644The Molecular Mechanisms Underlying the Hijack of Host Proteins by the 1918 Spanish Influenza Virus.
Auteurs : Qingliang Shen [États-Unis] ; Danyun Zeng [États-Unis] ; Baoyu Zhao [États-Unis] ; Veer S. Bhatt [États-Unis] ; Pingwei Li [États-Unis] ; Jae-Hyun Cho [États-Unis]Source :
- ACS chemical biology [ 1554-8937 ] ; 2017.
Descripteurs français
- KwdFr :
- Domaine d'homologie SRC, Humains, Liaison aux protéines, Pandémie de grippe de 1918-1919, Protéines proto-oncogènes c-crk (), Protéines proto-oncogènes c-crk (métabolisme), Protéines virales non structurales (), Protéines virales non structurales (métabolisme), Sites de fixation, Sous-type H1N1 du virus de la grippe A (), Sous-type H1N1 du virus de la grippe A (pathogénicité).
- MESH :
- métabolisme : Protéines proto-oncogènes c-crk, Protéines virales non structurales.
- pathogénicité : Sous-type H1N1 du virus de la grippe A.
- Domaine d'homologie SRC, Humains, Liaison aux protéines, Pandémie de grippe de 1918-1919, Protéines proto-oncogènes c-crk, Protéines virales non structurales, Sites de fixation, Sous-type H1N1 du virus de la grippe A.
English descriptors
- KwdEn :
- Binding Sites, Humans, Influenza A Virus, H1N1 Subtype (chemistry), Influenza A Virus, H1N1 Subtype (pathogenicity), Influenza Pandemic, 1918-1919, Protein Binding, Proto-Oncogene Proteins c-crk (chemistry), Proto-Oncogene Proteins c-crk (metabolism), Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (metabolism), src Homology Domains.
- MESH :
- chemical , chemistry : Proto-Oncogene Proteins c-crk, Viral Nonstructural Proteins.
- chemistry : Influenza A Virus, H1N1 Subtype.
- chemical , metabolism : Proto-Oncogene Proteins c-crk, Viral Nonstructural Proteins.
- pathogenicity : Influenza A Virus, H1N1 Subtype.
- Binding Sites, Humans, Influenza Pandemic, 1918-1919, Protein Binding, src Homology Domains.
Abstract
The 1918 Spanish influenza A virus (IAV) caused one of the most serious pandemics in history. The nonstructural protein 1 (NS1) of the 1918 IAV hijacks the interaction between human CrkII and JNK1. Little is, however, known about its molecular mechanism. Here, we performed X-ray crystallography, NMR relaxation dispersion experiment, and fluorescence spectroscopy to determine the structural, kinetic, and thermodynamic mechanisms underlying the hijacking of CrkII by 1918 IAV NS1. We observed that the interaction between a proline-rich motif in NS1 and the N-terminal SH3 domain of CrkII displays strikingly rapid kinetics and exceptionally high affinity with 100-fold faster kon and 3300-fold lower Kd compared to those for the CrkII-JNK1 interaction. These results provide molecular insight into the mechanism by which 1918 IAV NS1 hijacks CrkII and disrupts its interactions with critical cellular signaling proteins.
DOI: 10.1021/acschembio.7b00168
PubMed: 28368102
Affiliations:
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Bhatt</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843</wicri:regionArea><wicri:noRegion>Texas 77843</wicri:noRegion></affiliation></author><author><name sortKey="Li, Pingwei" sort="Li, Pingwei" uniqKey="Li P" first="Pingwei" last="Li">Pingwei Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843</wicri:regionArea><wicri:noRegion>Texas 77843</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Jae Hyun" sort="Cho, Jae Hyun" uniqKey="Cho J" first="Jae-Hyun" last="Cho">Jae-Hyun Cho</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843</wicri:regionArea><wicri:noRegion>Texas 77843</wicri:noRegion></affiliation></author></analytic><series><title level="j">ACS chemical biology</title><idno type="eISSN">1554-8937</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Binding Sites</term><term>Humans</term><term>Influenza A Virus, H1N1 Subtype (chemistry)</term><term>Influenza A Virus, H1N1 Subtype (pathogenicity)</term><term>Influenza Pandemic, 1918-1919</term><term>Protein Binding</term><term>Proto-Oncogene Proteins c-crk (chemistry)</term><term>Proto-Oncogene Proteins c-crk (metabolism)</term><term>Viral Nonstructural Proteins (chemistry)</term><term>Viral Nonstructural Proteins (metabolism)</term><term>src Homology Domains</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Domaine d'homologie SRC</term><term>Humains</term><term>Liaison aux protéines</term><term>Pandémie de grippe de 1918-1919</term><term>Protéines proto-oncogènes c-crk ()</term><term>Protéines proto-oncogènes c-crk (métabolisme)</term><term>Protéines virales non structurales ()</term><term>Protéines virales non structurales (métabolisme)</term><term>Sites de fixation</term><term>Sous-type H1N1 du virus de la grippe A ()</term><term>Sous-type H1N1 du virus de la grippe A (pathogénicité)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Proto-Oncogene Proteins c-crk</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Proto-Oncogene Proteins c-crk</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines proto-oncogènes c-crk</term><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Sous-type H1N1 du virus de la grippe A</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Humans</term><term>Influenza Pandemic, 1918-1919</term><term>Protein Binding</term><term>src Homology Domains</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Domaine d'homologie SRC</term><term>Humains</term><term>Liaison aux protéines</term><term>Pandémie de grippe de 1918-1919</term><term>Protéines proto-oncogènes c-crk</term><term>Protéines virales non structurales</term><term>Sites de fixation</term><term>Sous-type H1N1 du virus de la grippe A</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The 1918 Spanish influenza A virus (IAV) caused one of the most serious pandemics in history. The nonstructural protein 1 (NS1) of the 1918 IAV hijacks the interaction between human CrkII and JNK1. Little is, however, known about its molecular mechanism. Here, we performed X-ray crystallography, NMR relaxation dispersion experiment, and fluorescence spectroscopy to determine the structural, kinetic, and thermodynamic mechanisms underlying the hijacking of CrkII by 1918 IAV NS1. We observed that the interaction between a proline-rich motif in NS1 and the N-terminal SH3 domain of CrkII displays strikingly rapid kinetics and exceptionally high affinity with 100-fold faster k<sub>on</sub> and 3300-fold lower K<sub>d</sub> compared to those for the CrkII-JNK1 interaction. These results provide molecular insight into the mechanism by which 1918 IAV NS1 hijacks CrkII and disrupts its interactions with critical cellular signaling proteins.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Shen, Qingliang" sort="Shen, Qingliang" uniqKey="Shen Q" first="Qingliang" last="Shen">Qingliang Shen</name></noRegion><name sortKey="Bhatt, Veer S" sort="Bhatt, Veer S" uniqKey="Bhatt V" first="Veer S" last="Bhatt">Veer S. Bhatt</name><name sortKey="Cho, Jae Hyun" sort="Cho, Jae Hyun" uniqKey="Cho J" first="Jae-Hyun" last="Cho">Jae-Hyun Cho</name><name sortKey="Li, Pingwei" sort="Li, Pingwei" uniqKey="Li P" first="Pingwei" last="Li">Pingwei Li</name><name sortKey="Zeng, Danyun" sort="Zeng, Danyun" uniqKey="Zeng D" first="Danyun" last="Zeng">Danyun Zeng</name><name sortKey="Zhao, Baoyu" sort="Zhao, Baoyu" uniqKey="Zhao B" first="Baoyu" last="Zhao">Baoyu Zhao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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