View source for 7eno


==Mutant strain M3 of foot-and-mouth disease virus type O==
<StructureSection load='7eno' size='340' side='right'caption='[[7eno]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7eno]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Foot-and-mouth_disease_virus_O Foot-and-mouth disease virus O]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ENO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ENO 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]] 3.15&#8491;</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=7eno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eno OCA], [https://pdbe.org/7eno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eno RCSB], [https://www.ebi.ac.uk/pdbsum/7eno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eno ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G8JKC1_9PICO G8JKC1_9PICO] Associates with and induces structural rearrangements of intracellular membranes. Triggers host autophagy by interacting with host BECN1 and thereby promotes viral replication. Participates in viral replication and interacts with host DHX9. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3.[ARBA:ARBA00003578]  Covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. Acts as a genome-linked replication primer.[ARBA:ARBA00002573]  Cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, binds to viral RNA and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease.[ARBA:ARBA00004047]  Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome.[ARBA:ARBA00033732]  Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP1 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome.[ARBA:ARBA00033735]  Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. Capsid protein VP4 is released, capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm. After genome has been released, the channel shrinks.[ARBA:ARBA00033716]  Mediates self-processing of the polyprotein by a translational effect termed 'ribosome skipping'. Mechanistically, 2A-mediated cleavage occurs between the C-terminal glycine and the proline of the downstream protein 2B. In the case of foot-and-mouth disease virus, the 2A oligopeptide is post-translationally 'trimmed' from the C-terminus of the upstream protein 1D by 3C proteinase.[ARBA:ARBA00002616]  Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication.[ARBA:ARBA00003379]  RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated.[ARBA:ARBA00004027]
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== Publication Abstract from PubMed ==
Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals that causes a significant economic burden globally. Vaccination is the most effective FMD control strategy. However, FMD virus (FMDV) particles are prone to dissociate when appropriate physical or chemical conditions are unavailable, such as an incomplete cold chain. Such degraded vaccines result in compromised herd vaccination. Therefore, thermostable FMD particles are needed for use in vaccines. This study generated thermostable FMDV mutants (M3 and M10) by serial passages at high temperature, subsequent amplification, and purification. Both mutants contained an alanine-to-threonine mutation at position 13 in VP1 (A1013T), although M3 contained 3 additional mutations. The selected mutants showed improved stability and immunogenicity in neutralizing antibody titers, compared with the wild-type (wt) virus. The sequencing analysis and cryo-electron microscopy showed that the mutation of alanine to threonine at the 13th amino acid in the VP1 protein (A1013T) is critical for the capsid stability of FMDV. Virus-like particles containing A1013T (VLP(A1013T)) also showed significantly improved stability to heat treatment. This study demonstrated that Thr at the 13th amino acid of VP1 could stabilize the capsid of FMDV. Our findings will facilitate the development of a stable vaccine against FMDV serotype O. IMPORTANCE Foot-and-mouth disease (FMD) serotype O is one of the global epidemic serotypes and causes significant economic loss. Vaccination plays a key role in the prevention and control of FMD. However, the success of vaccination mainly depends on the quality of the vaccine. Here, the thermostable FMD virus (FMDV) mutants (M3 and M10) were selected through thermal screening at high temperatures with improved stability and immunogenicity compared with the wild-type virus. The results of multisequence alignment and cryo-electron microscopy (cryo-EM) analysis showed that the Thr substitution at the 13th amino acid in the VP1 protein is critical for the capsid stability of FMDV. For thermolabile type O FMDV, this major discovery will aid the development of its thermostable vaccine.

A Heat-Induced Mutation on VP1 of Foot-and-Mouth Disease Virus Serotype O Enhanced Capsid Stability and Immunogenicity.,Dong H, Lu Y, Zhang Y, Mu S, Wang N, Du P, Zhi X, Wen X, Wang X, Sun S, Zhang Y, Guo H J Virol. 2021 Jul 26;95(16):e0017721. doi: 10.1128/JVI.00177-21. Epub 2021 Jul , 26. PMID:34011545<ref>PMID:34011545</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 7eno" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Foot-and-mouth disease virus O]]
[[Category: Large Structures]]
[[Category: Dong H]]
[[Category: Lu Y]]