4c2i
From Proteopedia
(Difference between revisions)
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| - | + | ==Cryo-EM structure of Dengue virus serotype 1 complexed with Fab fragments of human antibody 1F4== | |
| - | + | <StructureSection load='4c2i' size='340' side='right' caption='[[4c2i]], [[Resolution|resolution]] 6.00Å' 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> | |
| - | ==Function== | + | </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> |
| + | <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://www.rcsb.org/pdb/explore.do?structureId=4c2i RCSB], [http://www.ebi.ac.uk/pdbsum/4c2i PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
[[http://www.uniprot.org/uniprot/Q7TGE4_9FLAV 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] [[http://www.uniprot.org/uniprot/G3F5K5_9FLAV 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] | [[http://www.uniprot.org/uniprot/Q7TGE4_9FLAV 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] [[http://www.uniprot.org/uniprot/G3F5K5_9FLAV 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] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:24421336</ref> | |
| - | + | ||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
*[[Antibody|Antibody]] | *[[Antibody|Antibody]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Dengue virus 1]] | [[Category: Dengue virus 1]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Alwis, R de | + | [[Category: Alwis, R de]] |
| - | [[Category: Fibriansah, G | + | [[Category: Fibriansah, G]] |
| - | [[Category: Harris, E | + | [[Category: Harris, E]] |
| - | [[Category: Ibarra, K D | + | [[Category: Ibarra, K D]] |
| - | [[Category: Junior, J E.Crowe | + | [[Category: Junior, J E.Crowe]] |
| - | [[Category: Kostyuchenko, V A | + | [[Category: Kostyuchenko, V A]] |
| - | [[Category: Lok, S M | + | [[Category: Lok, S M]] |
| - | [[Category: Ng, T S | + | [[Category: Ng, T S]] |
| - | [[Category: Silva, A de | + | [[Category: Silva, A de]] |
| - | [[Category: Smith, S A | + | [[Category: Smith, S A]] |
| - | [[Category: Tan, J L | + | [[Category: Tan, J L]] |
[[Category: E protein]] | [[Category: E protein]] | ||
[[Category: Neutralization]] | [[Category: Neutralization]] | ||
[[Category: Virus]] | [[Category: Virus]] | ||
Revision as of 02:56, 25 December 2014
Cryo-EM structure of Dengue virus serotype 1 complexed with Fab fragments of human antibody 1F4
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Categories: Dengue virus 1 | Homo sapiens | Alwis, R de | Fibriansah, G | Harris, E | Ibarra, K D | Junior, J E.Crowe | Kostyuchenko, V A | Lok, S M | Ng, T S | Silva, A de | Smith, S A | Tan, J L | E protein | Neutralization | Virus
