View source for 6weq


==DENV1 NS1 in complex with neutralizing 2B7 Fab fragment==
<StructureSection load='6weq' size='340' side='right'caption='[[6weq]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6weq]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_1 Dengue virus 1] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WEQ 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]] 3.2&#8491;</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6weq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6weq OCA], [https://pdbe.org/6weq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6weq RCSB], [https://www.ebi.ac.uk/pdbsum/6weq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6weq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9J7C6_9FLAV Q9J7C6_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]
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== Publication Abstract from PubMed ==
Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown. Here, we present three crystal structures of full-length dengue virus NS1 complexed with a flavivirus-cross-reactive, NS1-specific monoclonal antibody, 2B7, at resolutions between 2.89 and 3.96 angstroms. These structures reveal a protective mechanism by which two domains of NS1 are antagonized simultaneously. The NS1 wing domain mediates cell binding, whereas the beta-ladder triggers downstream events, both of which are required for dengue, Zika, and West Nile virus NS1-mediated endothelial dysfunction. These observations provide a mechanistic explanation for 2B7 protection against NS1-induced pathology and demonstrate the potential of one antibody to treat infections by multiple flaviviruses.

Structural basis for antibody inhibition of flavivirus NS1-triggered endothelial dysfunction.,Biering SB, Akey DL, Wong MP, Brown WC, Lo NTN, Puerta-Guardo H, Tramontini Gomes de Sousa F, Wang C, Konwerski JR, Espinosa DA, Bockhaus NJ, Glasner DR, Li J, Blanc SF, Juan EY, Elledge SJ, Mina MJ, Beatty PR, Smith JL, Harris E Science. 2021 Jan 8;371(6525):194-200. doi: 10.1126/science.abc0476. PMID:33414220<ref>PMID:33414220</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
*[[Nonstructural protein 3D structures|Nonstructural protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dengue virus 1]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Akey DL]]
[[Category: Smith JL]]