2r69

From Proteopedia

(Difference between revisions)

Revision as of 07:43, 25 October 2017

Crystal structure of Fab 1A1D-2 complexed with E-DIII of Dengue virus at 3.8 angstrom resolution

Structural highlights

2r69 is a 3 chain structure with sequence from Den26 and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	E protein (DEN26), immunoglobulin (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[POLG_DEN2U] prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated (By similarity). 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). Non-structural protein 1 is involved in virus replication and regulation of the innate immune response. Soluble and membrane-associated NS1 may activate human complement and induce host vascular leakage. This effect might explain the clinical manifestations of dengue hemorrhagic fever and dengue shock syndrome (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 degrees C, suggesting that the virus is in dynamic motion making hidden epitopes briefly available. A cryo-electron microscope image reconstruction of the virus:Fab complex showed large changes in the organization of the E protein that exposed the epitopes on two of the three E molecules in each of the 60 icosahedral asymmetric units of the virus. The changes in the structure of the viral surface are presumably responsible for inhibiting attachment to cells.

Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins.,Lok SM, Kostyuchenko V, Nybakken GE, Holdaway HA, Battisti AJ, Sukupolvi-Petty S, Sedlak D, Fremont DH, Chipman PR, Roehrig JT, Diamond MS, Kuhn RJ, Rossmann MG Nat Struct Mol Biol. 2008 Mar;15(3):312-7. Epub 2008 Feb 10. PMID:18264114^[1]

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

References

↑ Lok SM, Kostyuchenko V, Nybakken GE, Holdaway HA, Battisti AJ, Sukupolvi-Petty S, Sedlak D, Fremont DH, Chipman PR, Roehrig JT, Diamond MS, Kuhn RJ, Rossmann MG. Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Nat Struct Mol Biol. 2008 Mar;15(3):312-7. Epub 2008 Feb 10. PMID:18264114 doi:10.1038/nsmb.1382

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2r69"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Fab 1A1D-2 complexed with E-DIII of Dengue virus at 3.8 angstrom resolution==
 <StructureSection load='2r69' size='340' side='right' caption='[[2r69]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2r69]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Den26 Den26] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R69 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2R69 FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">E protein ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31634 DEN26]), immunoglobulin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2r69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r69 OCA], [http://pdbe.org/2r69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2r69 RCSB], [http://www.ebi.ac.uk/pdbsum/2r69 PDBsum]</span></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=2r69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r69 OCA], [http://pdbe.org/2r69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2r69 RCSB], [http://www.ebi.ac.uk/pdbsum/2r69 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2r69 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 37: / Line 38: @@
 [[Category: Diamond, M S]]
 [[Category: Fremont, D H]]
-[[Category: Holdaway,H A]]
+[[Category: Holdaway, H A]]
 [[Category: Kostyuchenko, V K]]
 [[Category: Kuhn, R J]]

2r69

From Proteopedia

Revision as of 07:43, 25 October 2017

Crystal structure of Fab 1A1D-2 complexed with E-DIII of Dengue virus at 3.8 angstrom resolution

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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