View source for 4x17


==JC Mad-1 polyomavirus VP1 in complex with GD1b oligosaccharide==
<StructureSection load='4x17' size='340' side='right'caption='[[4x17]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4x17]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/JC_polyomavirus JC polyomavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X17 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]] 1.75&#8491;</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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</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=4x17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x17 OCA], [https://pdbe.org/4x17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x17 RCSB], [https://www.ebi.ac.uk/pdbsum/4x17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x17 ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/VP1_POVJC VP1_POVJC] Forms an icosahedral capsid with a T=7 symmetry and a 40 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Interacts with a N-linked glycoprotein containing terminal alpha(2-6)-linked sialic acids on the cell surface to provide virion attachment to target cell. The serotonergic receptor 5HT2AR also acts as a cellular receptor for JCV on human glial cells. Once attached, the virions enter predominantly by a ligand-inducible clathrin-dependent pathway and traffic to the ER. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. In late phase of infection, neo-synthesized VP1 encapsulates replicated genomic DNA at nuclear domains called promyelocytic leukemia (PML) bodies, and participates in rearranging nucleosomes around the viral DNA.<ref>PMID:10666259</ref> 
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== Publication Abstract from PubMed ==
The human JC polyomavirus (JCPyV) establishes an asymptomatic, persistent infection in the kidney of the majority of the population, and is the causative agent of the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals. The Mad-1 strain of JCPyV, a brain isolate, was shown earlier to require alpha2,6-linked sialic acid on the LSTc glycan for attachment to host cells. In contrast, a JCPyV kidney isolate Type 3 strain, "WT3", has been reported to interact with sialic acid-containing gangliosides, but the role of these glycans in JCPyV infection has remained unclear. To help rationalize these findings and probe the effects of strain-specific differences on receptor binding, we performed a comprehensive analysis of the glycan receptor specificities of these two representative JCPyV strains using high-resolution X-ray crystallography and NMR spectroscopy, and correlated these data with infectivity assays. We show here that capsid proteins of Mad-1 and WT3 JCPyV can both engage LSTc as well as multiple sialylated gangliosides. However, the binding affinities exhibit subtle differences, with the highest affinity observed for LSTc. Engagement of LSTc is a prerequisite for functional receptor engagement while the weaker-binding gangliosides are not required for productive infection. Our findings highlight the complexity of virus-carbohydrate interactions and demonstrate that subtle differences in binding affinities, rather than the binding event alone, help determine tissue tropism and viral pathogenesis. IMPORTANCE: Viral infection is initiated by attachment to receptors on host cells, and this event plays an important role in viral disease. We investigated the receptor-binding properties of human JC polyomavirus (JCPyV), a virus that resides in the kidney of the majority of the population and can cause the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML) in the brain of immunosuppressed individuals. JCPyV has been reported to interact with multiple carbohydrate receptors, and we sought to clarify how the interactions between JCPyV and cellular carbohydrate receptors influenced infection. Here we demonstrate that JCPyV can engage numerous sialylated carbohydrate receptors. However, the virus displays preferential binding to LSTc, and only LSTc mediates a productive infection. Our findings demonstrate that subtle differences in binding affinity, rather than receptor engagement alone, are a key determinant of viral infection.

Increased Affinity of JC Polyomavirus Capsid for LSTc Over Other Sialylated Glycans Is a Major Determinant of Infectivity.,Stroh LJ, Maginnis MS, Blaum BS, Nelson CD, Neu U, Gee GV, O'Hara BA, Motamedi N, DiMaio D, Atwood WJ, Stehle T J Virol. 2015 Apr 8. pii: JVI.00489-15. PMID:25855729<ref>PMID:25855729</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 4x17" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: JC polyomavirus]]
[[Category: Large Structures]]
[[Category: Stehle T]]
[[Category: Stroh LJ]]