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4c2i

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Revision as of 18:59, 10 April 2020

Cryo-EM structure of Dengue virus serotype 1 complexed with Fab fragments of human antibody 1F4

4c2i, resolution 6.00Å

Structural highlights

4c2i is a 10 chain structure with sequence from Dengue virus 1 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[Q7TGE4_9FLAV] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS027287_004_099774] [G3F5K5_9FLAV] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS026470_004_099774]

Publication Abstract from PubMed

Dengue virus (DENV), which consists of four serotypes (DENV1-4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross-reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype-specific and bind to quaternary structure-dependent epitopes. We determined the structure of DENV1 complexed with Fab fragments of a highly potent HMAb 1F4 to 6 A resolution by cryo-EM. Although HMAb 1F4 appeared to bind to virus and not E proteins in ELISAs in the previous study, our structure showed that the epitope is located within an envelope (E) protein monomer, and not across neighboring E proteins. The Fab molecules bind to domain I (DI), and DI-DII hinge of the E protein. We also showed that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner. The structure reveals the mechanism by which this potent and specific antibody blocks viral infection.

A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface.,Fibriansah G, Tan JL, Smith SA, de Alwis AR, Ng TS, Kostyuchenko VA, Ibarra KD, Wang J, Harris E, de Silva A, Crowe JE Jr, Lok SM EMBO Mol Med. 2014 Jan 13. PMID:24421336^[1]

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

References

↑ Fibriansah G, Tan JL, Smith SA, de Alwis AR, Ng TS, Kostyuchenko VA, Ibarra KD, Wang J, Harris E, de Silva A, Crowe JE Jr, Lok SM. A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface. EMBO Mol Med. 2014 Jan 13. PMID:24421336 doi:http://dx.doi.org/10.1002/emmm.201303404

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4c2i"

@@ Line 3: / Line 3: @@
 <SX load='4c2i' size='340' side='right' viewer='molstar' caption='[[4c2i]], [[Resolution|resolution]] 6.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4c2i]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_1 Dengue virus 1] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C2I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C2I FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4c2i]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_1 Dengue virus 1] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C2I OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4C2I FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4c2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c2i OCA], [http://pdbe.org/4c2i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c2i RCSB], [http://www.ebi.ac.uk/pdbsum/4c2i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c2i ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=4c2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c2i OCA], [http://pdbe.org/4c2i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c2i RCSB], [http://www.ebi.ac.uk/pdbsum/4c2i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c2i ProSAT]</span></td></tr>
 </table>
 == Function ==

4c2i

From Proteopedia

Revision as of 18:59, 10 April 2020

Cryo-EM structure of Dengue virus serotype 1 complexed with Fab fragments of human antibody 1F4

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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