View source for 6lhk


==The cryo-EM structure of coxsackievirus A16 mature virion in complex with Fab 18A7==
<SX load='6lhk' size='340' side='right' viewer='molstar' caption='[[6lhk]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lhk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxsackievirus_A16 Coxsackievirus A16]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LHK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LHK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SPH:SPHINGOSINE'>SPH</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=6lhk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lhk OCA], [https://pdbe.org/6lhk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lhk RCSB], [https://www.ebi.ac.uk/pdbsum/6lhk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lhk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POLG_CX16T POLG_CX16T] Protein VP1: Forms, together with VP2 and VP3, an icosahedral capsid (pseudo T=3), 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome. Protein VP1 mainly forms the vertices of the capsid. VP1 interacts with host cell receptor to provide virion attachment to target cell. After binding to its receptor, the capsid undergoes conformational changes. VP1 N-terminus (that contains an amphipathic alpha-helix) is externalized, VP4 is released and together, they shape a virion-cell connecting channel and a pore in the host membrane through which RNase-protected transfer of the viral genome takes place. After genome has been released, the channel shrinks (By similarity).  Protein VP2: Forms, together with VP1 and VP3, an icosahedral capsid (pseudo T=3), 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).  Protein VP3: Forms, together with VP1 and VP2, an icosahedral capsid (pseudo T=3), 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).  Protein VP4: Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. VP4 is released, VP1 N-terminus is externalized, and together, they shape a virion-cell connecting channel and a pore in the host membrane through which RNase-protected transfer of the viral genome takes place. After genome has been released, the channel shrinks (By similarity).  Protein VP0: Protein VP0: VP0 precursor is a component of immature procapsids, which gives rise to VP4 and VP2 after maturation. Allows the capsid to remain inactive before the maturation step (By similarity).  Protease 2A: cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut off the capped cellular mRNA transcription (By similarity).  Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity).  Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).  Protein 3A, via its hydrophobic domain, serves as membrane anchor. It also inhibits endoplasmic reticulum-to-Golgi transport (By similarity).  Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity).  RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).
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== Publication Abstract from PubMed ==
Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific neutralizing monoclonal antibodies (nAbs) with therapeutic potential: 18A7, 14B10, and NA9D7. We present atomic structures of these nAbs bound to all three viral particle forms-the mature virion, A-particle, and empty particle-and show that each Fab can simultaneously occupy the mature virion. Additionally, 14B10 or NA9D7 provide 100% protection against lethal CVA16 infection in a neonatal mouse model. 18A7 binds to a non-conserved epitope present in all three particles, whereas 14B10 and NA9D7 recognize broad protective epitopes but only bind the mature virion. NA9D7 targets an immunodominant site, which may overlap the receptor-binding site. These findings indicate that CVA16 vaccines should be based on mature virions and that these antibodies could be used to discriminate optimal virion-based immunogens.

Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16.,He M, Xu L, Zheng Q, Zhu R, Yin Z, Zha Z, Lin Y, Yang L, Huang Y, Ye X, Li S, Hou W, Wu Y, Han J, Liu D, Li Z, Chen Z, Yu H, Que Y, Wang Y, Yan X, Zhang J, Gu Y, Zhou ZH, Cheng T, Li S, Xia N Cell Host Microbe. 2020 Feb 12;27(2):249-261.e5. doi: 10.1016/j.chom.2020.01.003., Epub 2020 Feb 5. PMID:32027857<ref>PMID:32027857</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6lhk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
== References ==
<references/>
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[[Category: Coxsackievirus A16]]
[[Category: Large Structures]]
[[Category: Cheng T]]
[[Category: He MZ]]
[[Category: Li SW]]
[[Category: Xu LF]]
[[Category: Yin ZC]]
[[Category: Zheng QB]]
[[Category: Zhu R]]