7ajp: Difference between revisions
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==Crystal Structure of Human Adenovirus 56 Fiber Knob== | |||
<StructureSection load='7ajp' size='340' side='right'caption='[[7ajp]], [[Resolution|resolution]] 1.38Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7ajp]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_adenovirus_56 Human adenovirus 56]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AJP FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.382018Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ajp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ajp OCA], [https://pdbe.org/7ajp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ajp RCSB], [https://www.ebi.ac.uk/pdbsum/7ajp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ajp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/R9RU05_9ADEN R9RU05_9ADEN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human adenovirus species D (HAdV-D) types are currently being explored as vaccine vectors for coronavirus disease 2019 (COVID-19) and other severe infectious diseases. The efficacy of such vector-based vaccines depends on functional interactions with receptors on host cells. Adenoviruses of different species are assumed to enter host cells mainly by interactions between the knob domain of the protruding fiber capsid protein and cellular receptors. Using a cell-based receptor-screening assay, we identified CD46 as a receptor for HAdV-D56. The function of CD46 was validated in infection experiments using cells lacking and overexpressing CD46, and by competition infection experiments using soluble CD46. Remarkably, unlike HAdV-B types that engage CD46 through interactions with the knob domain of the fiber protein, HAdV-D types infect host cells through a direct interaction between CD46 and the hexon protein. Soluble hexon proteins (but not fiber knob) inhibited HAdV-D56 infection, and surface plasmon analyses demonstrated that CD46 binds to HAdV-D hexon (but not fiber knob) proteins. Cryoelectron microscopy analysis of the HAdV-D56 virion-CD46 complex confirmed the interaction and showed that CD46 binds to the central cavity of hexon trimers. Finally, soluble CD46 inhibited infection by 16 out of 17 investigated HAdV-D types, suggesting that CD46 is an important receptor for a large group of adenoviruses. In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors. | |||
Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46.,Persson BD, John L, Rafie K, Strebl M, Frangsmyr L, Ballmann MZ, Mindler K, Havenga M, Lemckert A, Stehle T, Carlson LA, Arnberg N Proc Natl Acad Sci U S A. 2021 Jan 19;118(3). pii: 2020732118. doi:, 10.1073/pnas.2020732118. PMID:33384338<ref>PMID:33384338</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7ajp" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human adenovirus 56]] | |||
[[Category: Large Structures]] | |||
[[Category: Mindler K]] | |||
[[Category: Stehle T]] | |||
[[Category: Strebl M]] | |||
Latest revision as of 15:10, 1 February 2024
Crystal Structure of Human Adenovirus 56 Fiber KnobCrystal Structure of Human Adenovirus 56 Fiber Knob
Structural highlights
FunctionPublication Abstract from PubMedHuman adenovirus species D (HAdV-D) types are currently being explored as vaccine vectors for coronavirus disease 2019 (COVID-19) and other severe infectious diseases. The efficacy of such vector-based vaccines depends on functional interactions with receptors on host cells. Adenoviruses of different species are assumed to enter host cells mainly by interactions between the knob domain of the protruding fiber capsid protein and cellular receptors. Using a cell-based receptor-screening assay, we identified CD46 as a receptor for HAdV-D56. The function of CD46 was validated in infection experiments using cells lacking and overexpressing CD46, and by competition infection experiments using soluble CD46. Remarkably, unlike HAdV-B types that engage CD46 through interactions with the knob domain of the fiber protein, HAdV-D types infect host cells through a direct interaction between CD46 and the hexon protein. Soluble hexon proteins (but not fiber knob) inhibited HAdV-D56 infection, and surface plasmon analyses demonstrated that CD46 binds to HAdV-D hexon (but not fiber knob) proteins. Cryoelectron microscopy analysis of the HAdV-D56 virion-CD46 complex confirmed the interaction and showed that CD46 binds to the central cavity of hexon trimers. Finally, soluble CD46 inhibited infection by 16 out of 17 investigated HAdV-D types, suggesting that CD46 is an important receptor for a large group of adenoviruses. In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors. Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46.,Persson BD, John L, Rafie K, Strebl M, Frangsmyr L, Ballmann MZ, Mindler K, Havenga M, Lemckert A, Stehle T, Carlson LA, Arnberg N Proc Natl Acad Sci U S A. 2021 Jan 19;118(3). pii: 2020732118. doi:, 10.1073/pnas.2020732118. PMID:33384338[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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