3jd7: Difference between revisions

No edit summary
No edit summary
 
Line 3: Line 3:
<SX load='3jd7' size='340' side='right' viewer='molstar' caption='[[3jd7]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
<SX load='3jd7' size='340' side='right' viewer='molstar' caption='[[3jd7]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3jd7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxsackievirus_b3 Coxsackievirus b3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JD7 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3jd7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxsackievirus_B3 Coxsackievirus B3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JD7 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=3jd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jd7 OCA], [https://pdbe.org/3jd7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jd7 RCSB], [https://www.ebi.ac.uk/pdbsum/3jd7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jd7 ProSAT]</span></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=3jd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jd7 OCA], [https://pdbe.org/3jd7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jd7 RCSB], [https://www.ebi.ac.uk/pdbsum/3jd7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jd7 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/POLG_CXB3W POLG_CXB3W]] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (By similarity)VP0 precursor is a component of immature procapsids (By similarity).  Protein 2A is a 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 down 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).  Protein 3C is a 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 co-operatively to the protease (By similarity).  RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).
[https://www.uniprot.org/uniprot/Q5UEA3_9ENTO Q5UEA3_9ENTO] Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU (By similarity). The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome (By similarity). Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity). During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions.[ARBA:ARBA00024846] Capsid protein VP0: Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation. Allows the capsid to remain inactive before the maturation step.[RuleBase:RU364118]  Capsid protein VP1: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome. Capsid protein VP1 mainly forms the vertices of the capsid. Capsid protein VP1 interacts with host cell receptor to provide virion attachment to target host cells. This attachment induces virion internalization. Tyrosine kinases are probably involved in the entry process. After binding to its receptor, the capsid undergoes conformational changes. Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized. Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm. After genome has been released, the channel shrinks.[RuleBase:RU364118]  Capsid protein VP2: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome.[RuleBase:RU364118]  Capsid protein VP3: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome.[RuleBase:RU364118]  Capsid protein VP4: 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.[RuleBase:RU364118] Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity). Allows the capsid to remain inactive before the maturation step.[ARBA:ARBA00025202] Protease 2A: Cysteine protease that cleaves viral polyprotein and specific host proteins.[RuleBase:RU364118]  Protease 3C: Major viral protease that mediates proteolytic processing of the polyprotein. Cleaves host EIF5B, contributing to host translation shutoff. Cleaves also host PABPC1, contributing to host translation shutoff.[RuleBase:RU364118] Protein 2B: 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.[RuleBase:RU364118] Protein 2C: Induces and associates with structural rearrangements of intracellular membranes. 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.[RuleBase:RU364118] Protein 3A: Localizes the viral replication complex to the surface of membranous vesicles. It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction. This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface.[RuleBase:RU364118] Protein 3AB: Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity.[RuleBase:RU364118]  Protein 3CD: Involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the 5'UTR of the viral genome.[RuleBase:RU364118] RNA-directed RNA polymerase: Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. 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.[RuleBase:RU364118]  Viral protein genome-linked: acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU. The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome.[RuleBase:RU364118]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Many nonenveloped viruses engage host receptors that initiate capsid conformational changes necessary for genome release. Structural studies on the mechanisms of picornavirus entry have relied on in vitro approaches of virus incubated at high temperatures or with excess receptor molecules to trigger the entry intermediate or A-particle. We have induced the coxsackievirus B3 entry intermediate by triggering the virus with full-length receptors embedded in lipid bilayer nanodiscs. These asymmetrically formed A-particles were reconstructed using cryo-electron microscopy and a direct electron detector. These first high-resolution structures of a picornavirus entry intermediate captured at a membrane with and without imposing icosahedral symmetry (3.9 and 7.8 A, respectively) revealed a novel A-particle that is markedly different from the classical A-particles. The asymmetric receptor binding triggers minimal global capsid expansion but marked local conformational changes at the site of receptor interaction. In addition, viral proteins extrude from the capsid only at the site of extensive protein remodeling adjacent to the nanodisc. Thus, the binding of the receptor triggers formation of a unique site in preparation for genome release.
 
The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs.,Lee H, Shingler KL, Organtini LJ, Ashley RE, Makhov AM, Conway JF, Hafenstein S Sci Adv. 2016 Aug 24;2(8):e1501929. doi: 10.1126/sciadv.1501929. eCollection 2016, Aug. PMID:27574701<ref>PMID:27574701</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3jd7" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</SX>
</SX>
[[Category: Coxsackievirus b3]]
[[Category: Coxsackievirus B3]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Ashley, R E]]
[[Category: Ashley RE]]
[[Category: Conway, J F]]
[[Category: Conway JF]]
[[Category: Hafenstein, S]]
[[Category: Hafenstein S]]
[[Category: Lee, H]]
[[Category: Lee H]]
[[Category: Makhov, A M]]
[[Category: Makhov AM]]
[[Category: Organtini, L J]]
[[Category: Organtini LJ]]
[[Category: Shingler, K L]]
[[Category: Shingler KL]]
[[Category: Entry intermediate]]
[[Category: Picornavirus]]
[[Category: Virus]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA