A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses
Identifieur interne : 000111 ( PascalFrancis/Checkpoint ); précédent : 000110; suivant : 000112A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses
Auteurs : KAILANG WU [États-Unis] ; LANG CHEN [États-Unis] ; GUIQING PENG [États-Unis] ; WENBO ZHOU [États-Unis] ; Christopher A. Pennell [États-Unis] ; Louis M. Mansky [États-Unis] ; Robert J. Geraghty [États-Unis] ; FANG LI [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2011.
Descripteurs français
- Pascal (Inist)
- Wicri :
English descriptors
- KwdEn :
Abstract
How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
Pascal:11-0268018Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses</title><author><name sortKey="Kailang Wu" sort="Kailang Wu" uniqKey="Kailang Wu" last="Kailang Wu">KAILANG WU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Lang Chen" sort="Lang Chen" uniqKey="Lang Chen" last="Lang Chen">LANG CHEN</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Guiqing Peng" sort="Guiqing Peng" uniqKey="Guiqing Peng" last="Guiqing Peng">GUIQING PENG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Wenbo Zhou" sort="Wenbo Zhou" uniqKey="Wenbo Zhou" last="Wenbo Zhou">WENBO ZHOU</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Drug Design, University of Minnesota</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Pennell, Christopher A" sort="Pennell, Christopher A" uniqKey="Pennell C" first="Christopher A." last="Pennell">Christopher A. Pennell</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Cancer Center, Center for Immunology, University of Minnesota</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Mansky, Louis M" sort="Mansky, Louis M" uniqKey="Mansky L" first="Louis M." last="Mansky">Louis M. Mansky</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institute for Molecular Virology and Departments of Diagnostic and Biological Sciences and Microbiology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Geraghty, Robert J" sort="Geraghty, Robert J" uniqKey="Geraghty R" first="Robert J." last="Geraghty">Robert J. Geraghty</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Drug Design, University of Minnesota</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Fang Li" sort="Fang Li" uniqKey="Fang Li" last="Fang Li">FANG LI</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">11-0268018</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 11-0268018 INIST</idno><idno type="RBID">Pascal:11-0268018</idno><idno type="wicri:Area/PascalFrancis/Corpus">000106</idno><idno type="wicri:Area/PascalFrancis/Curation">000882</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000111</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000111</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses</title><author><name sortKey="Kailang Wu" sort="Kailang Wu" uniqKey="Kailang Wu" last="Kailang Wu">KAILANG WU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Lang Chen" sort="Lang Chen" uniqKey="Lang Chen" last="Lang Chen">LANG CHEN</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Guiqing Peng" sort="Guiqing Peng" uniqKey="Guiqing Peng" last="Guiqing Peng">GUIQING PENG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Wenbo Zhou" sort="Wenbo Zhou" uniqKey="Wenbo Zhou" last="Wenbo Zhou">WENBO ZHOU</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Drug Design, University of Minnesota</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Pennell, Christopher A" sort="Pennell, Christopher A" uniqKey="Pennell C" first="Christopher A." last="Pennell">Christopher A. Pennell</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Cancer Center, Center for Immunology, University of Minnesota</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Mansky, Louis M" sort="Mansky, Louis M" uniqKey="Mansky L" first="Louis M." last="Mansky">Louis M. Mansky</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institute for Molecular Virology and Departments of Diagnostic and Biological Sciences and Microbiology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Geraghty, Robert J" sort="Geraghty, Robert J" uniqKey="Geraghty R" first="Robert J." last="Geraghty">Robert J. Geraghty</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Drug Design, University of Minnesota</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author><author><name sortKey="Fang Li" sort="Fang Li" uniqKey="Fang Li" last="Fang Li">FANG LI</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Minneapolis, Minnesota 55455</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Angiotensin</term><term>Enzyme</term><term>Human</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Homme</term><term>Angiotensine</term><term>Enzyme</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term><term>Enzyme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0022-538X</s0></fA01><fA03 i2="1"><s0>J. virol.</s0></fA03><fA05><s2>85</s2></fA05><fA06><s2>11</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses</s1></fA08><fA11 i1="01" i2="1"><s1>KAILANG WU</s1></fA11><fA11 i1="02" i2="1"><s1>LANG CHEN</s1></fA11><fA11 i1="03" i2="1"><s1>GUIQING PENG</s1></fA11><fA11 i1="04" i2="1"><s1>WENBO ZHOU</s1></fA11><fA11 i1="05" i2="1"><s1>PENNELL (Christopher A.)</s1></fA11><fA11 i1="06" i2="1"><s1>MANSKY (Louis M.)</s1></fA11><fA11 i1="07" i2="1"><s1>GERAGHTY (Robert J.)</s1></fA11><fA11 i1="08" i2="1"><s1>FANG LI</s1></fA11><fA14 i1="01"><s1>Department of Pharmacology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></fA14><fA14 i1="02"><s1>Center for Drug Design, University of Minnesota</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></fA14><fA14 i1="03"><s1>Cancer Center, Center for Immunology, University of Minnesota</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>5 aut.</sZ></fA14><fA14 i1="04"><s1>Institute for Molecular Virology and Departments of Diagnostic and Biological Sciences and Microbiology, University of Minnesota Medical School</s1><s2>Minneapolis, Minnesota 55455</s2><s3>USA</s3><sZ>6 aut.</sZ></fA14><fA20><s1>5331-5337</s1></fA20><fA21><s1>2011</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>13592</s2><s5>354000192117060100</s5></fA43><fA44><s0>0000</s0><s1>© 2011 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>33 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>11-0268018</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Journal of virology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.</s0></fC01><fC02 i1="01" i2="X"><s0>002A05C10</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Homme</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Human</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Hombre</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Angiotensine</s0><s2>NK</s2><s2>FR</s2><s5>05</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Angiotensin</s0><s2>NK</s2><s2>FR</s2><s5>05</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Angiotensina</s0><s2>NK</s2><s2>FR</s2><s5>05</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Enzyme</s0><s2>FE</s2><s5>06</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Enzyme</s0><s2>FE</s2><s5>06</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Enzima</s0><s2>FE</s2><s5>06</s5></fC03><fN21><s1>178</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Kailang Wu" sort="Kailang Wu" uniqKey="Kailang Wu" last="Kailang Wu">KAILANG WU</name></noRegion><name sortKey="Fang Li" sort="Fang Li" uniqKey="Fang Li" last="Fang Li">FANG LI</name><name sortKey="Geraghty, Robert J" sort="Geraghty, Robert J" uniqKey="Geraghty R" first="Robert J." last="Geraghty">Robert J. Geraghty</name><name sortKey="Guiqing Peng" sort="Guiqing Peng" uniqKey="Guiqing Peng" last="Guiqing Peng">GUIQING PENG</name><name sortKey="Lang Chen" sort="Lang Chen" uniqKey="Lang Chen" last="Lang Chen">LANG CHEN</name><name sortKey="Mansky, Louis M" sort="Mansky, Louis M" uniqKey="Mansky L" first="Louis M." last="Mansky">Louis M. Mansky</name><name sortKey="Pennell, Christopher A" sort="Pennell, Christopher A" uniqKey="Pennell C" first="Christopher A." last="Pennell">Christopher A. Pennell</name><name sortKey="Wenbo Zhou" sort="Wenbo Zhou" uniqKey="Wenbo Zhou" last="Wenbo Zhou">WENBO ZHOU</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/PascalFrancis/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000111 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PascalFrancis/Checkpoint/biblio.hfd -nk 000111 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= PascalFrancis
|étape= Checkpoint
|type= RBID
|clé= Pascal:11-0268018
|texte= A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses
}}
| This area was generated with Dilib version V0.6.33. |  |