7k22: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==== | ==Murine polyomavirus pentavalent capsomer with 8A7H5 Fab, subparticle reconstruction== | ||
<StructureSection load='7k22' size='340' side='right'caption='[[7k22]]' scene=''> | <StructureSection load='7k22' size='340' side='right'caption='[[7k22]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[7k22]] is a 15 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus_polyomavirus_1 Mus musculus polyomavirus 1] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K22 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</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=7k22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k22 OCA], [https://pdbe.org/7k22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k22 RCSB], [https://www.ebi.ac.uk/pdbsum/7k22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k22 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A247D727_POVM1 A0A247D727_POVM1] Forms an icosahedral capsid with a T=7 symmetry.[PIRNR:PIRNR003376] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
JCPyV polyomavirus, a member of the human virome, causes Progressive Multifocal Leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo EM and a custom sub-particle refinement approach, we resolved an MuPyV:Fab complex map to 3.2 A resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation. | |||
Antibody escape by polyomavirus capsid mutation facilitates neurovirulence.,Lauver MD, Goetschius DJ, Netherby-Winslow CS, Ayers KN, Jin G, Haas DG, Frost EL, Cho SH, Bator C, Bywaters SM, Christensen ND, Hafenstein SL, Lukacher AE Elife. 2020 Sep 17;9. pii: 61056. doi: 10.7554/eLife.61056. PMID:32940605<ref>PMID:32940605</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7k22" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus polyomavirus 1]] | ||
[[Category: Rattus norvegicus]] | |||
[[Category: Goetschius DJ]] | |||
[[Category: Hafenstein SL]] | |||
Latest revision as of 16:37, 6 November 2024
Murine polyomavirus pentavalent capsomer with 8A7H5 Fab, subparticle reconstructionMurine polyomavirus pentavalent capsomer with 8A7H5 Fab, subparticle reconstruction
Structural highlights
FunctionA0A247D727_POVM1 Forms an icosahedral capsid with a T=7 symmetry.[PIRNR:PIRNR003376] Publication Abstract from PubMedJCPyV polyomavirus, a member of the human virome, causes Progressive Multifocal Leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo EM and a custom sub-particle refinement approach, we resolved an MuPyV:Fab complex map to 3.2 A resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation. Antibody escape by polyomavirus capsid mutation facilitates neurovirulence.,Lauver MD, Goetschius DJ, Netherby-Winslow CS, Ayers KN, Jin G, Haas DG, Frost EL, Cho SH, Bator C, Bywaters SM, Christensen ND, Hafenstein SL, Lukacher AE Elife. 2020 Sep 17;9. pii: 61056. doi: 10.7554/eLife.61056. PMID:32940605[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||