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3nxd

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Revision as of 09:54, 30 January 2019

JC polyomavirus VP1 in complex with LSTc

Structural highlights

3nxd is a 5 chain structure with sequence from Human polyomavirus (type jc). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Related:	3bwr, 1vps, 3nxg
Gene:	VP1 (Human polyomavirus (type JC))
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

Publication Abstract from PubMed

The human JC polyomavirus (JCV) causes a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML), in immunocompromised individuals. Current treatment options for PML are inadequate. Sialylated oligosaccharides and the serotonin receptor are known to be necessary for JCV entry, but the molecular interactions underlying JCV attachment remain unknown. Using glycan array screening and viral infectivity assays, we identify a linear sialylated pentasaccharide with the sequence NeuNAc-alpha2,6-Gal-beta1,4-GlcNAc-beta1,3-Gal-beta1,4-Glc (LSTc) present on host glycoproteins and glycolipids as a specific JCV recognition motif. The crystal structure of the JCV capsid protein VP1 was solved alone and in complex with LSTc. It reveals extensive interactions with the terminal sialic acid of the LSTc motif and specific recognition of an extended conformation of LSTc. Mutations in the JCV oligosaccharide-binding sites abolish cell attachment, viral spread, and infectivity, further validating the importance of this interaction. Our findings provide a powerful platform for the development of antiviral compounds.

Structure-function analysis of the human JC polyomavirus establishes the LSTc pentasaccharide as a functional receptor motif.,Neu U, Maginnis MS, Palma AS, Stroh LJ, Nelson CD, Feizi T, Atwood WJ, Stehle T Cell Host Microbe. 2010 Oct 21;8(4):309-19. PMID:20951965^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pho MT, Ashok A, Atwood WJ. JC virus enters human glial cells by clathrin-dependent receptor-mediated endocytosis. J Virol. 2000 Mar;74(5):2288-92. PMID:10666259
↑ Neu U, Maginnis MS, Palma AS, Stroh LJ, Nelson CD, Feizi T, Atwood WJ, Stehle T. Structure-function analysis of the human JC polyomavirus establishes the LSTc pentasaccharide as a functional receptor motif. Cell Host Microbe. 2010 Oct 21;8(4):309-19. PMID:20951965 doi:10.1016/j.chom.2010.09.004

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3nxd"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3nxd]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_polyomavirus_(type_jc) Human polyomavirus (type jc)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NXD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bwr|3bwr]], [[1vps|1vps]], [[3nxg|3nxg]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10632 Human polyomavirus (type JC)])</td></tr>

3nxd

From Proteopedia

Revision as of 09:54, 30 January 2019

JC polyomavirus VP1 in complex with LSTc

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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