4gxx

From Proteopedia

(Difference between revisions)

Revision as of 19:25, 4 August 2016

Crystal structure of the "avianized" 1918 influenza virus hemagglutinin

Structural highlights

4gxx is a 6 chain structure with sequence from I18a0. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4gxu, 4gxv
Gene:	HA (I18A0)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HEMA_I18A0] Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore (By similarity).

Publication Abstract from PubMed

Most monoclonal antibodies (mAbs) to the influenza A virus hemagglutinin (HA) head domain exhibit very limited breadth of inhibitory activity due to antigenic drift in field strains. However, mAb 1F1, isolated from a 1918 influenza pandemic survivor, inhibits select human H1 viruses (1918, 1943, 1947, and 1977 isolates). The crystal structure of 1F1 in complex with the 1918 HA shows that 1F1 contacts residues that are classically defined as belonging to three distinct antigenic sites, Sa, Sb and Ca(2). The 1F1 heavy chain also reaches into the receptor binding site (RBS) and interacts with residues that contact sialoglycan receptors and determine HA receptor specificity. The 1F1 epitope is remarkably similar to the previously described murine HC63 H3 epitope, despite significant sequence differences between H1 and H3 HAs. Both antibodies potently inhibit receptor binding, but only HC63 can block the pH-induced conformational changes in HA that drive membrane fusion. Contacts within the RBS suggested that 1F1 may be sensitive to changes that alter HA receptor binding activity. Affinity assays confirmed that sequence changes that switch the HA to avian receptor specificity affect binding of 1F1 and a mAb possessing a closely related heavy chain, 1I20. To characterize 1F1 cross-reactivity, additional escape mutant selection and site-directed mutagenesis were performed. Residues 190 and 227 in the 1F1 epitope were found to be critical for 1F1 reactivity towards 1918, 1943 and 1977 HAs, as well as for 1I20 reactivity towards the 1918 HA. Therefore, 1F1 heavy-chain interactions with conserved RBS residues likely contribute to its ability to inhibit divergent HAs.

Influenza Human Monoclonal Antibody 1F1 Interacts with Three Major Antigenic Sites and Residues Mediating Human Receptor Specificity in H1N1 Viruses.,Tsibane T, Ekiert DC, Krause JC, Martinez O, Crowe JE Jr, Wilson IA, Basler CF PLoS Pathog. 2012 Dec;8(12):e1003067. doi: 10.1371/journal.ppat.1003067. Epub, 2012 Dec 6. PMID:23236279^[1]

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

References

↑ Tsibane T, Ekiert DC, Krause JC, Martinez O, Crowe JE Jr, Wilson IA, Basler CF. Influenza Human Monoclonal Antibody 1F1 Interacts with Three Major Antigenic Sites and Residues Mediating Human Receptor Specificity in H1N1 Viruses. PLoS Pathog. 2012 Dec;8(12):e1003067. doi: 10.1371/journal.ppat.1003067. Epub, 2012 Dec 6. PMID:23236279 doi:http://dx.doi.org/10.1371/journal.ppat.1003067

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/4gxx"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the "avianized" 1918 influenza virus hemagglutinin==
 <StructureSection load='4gxx' size='340' side='right' caption='[[4gxx]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4gxx]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/brevig_mission/1/1918(h1n1)) Influenza a virus (a/brevig mission/1/1918(h1n1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GXX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4gxx]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/I18a0 I18a0]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GXX FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gxu|4gxu]], [[4gxv|4gxv]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=88776 Influenza A virus (A/Brevig Mission/1/1918(H1N1))])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=88776 I18A0])</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=4gxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gxx RCSB], [http://www.ebi.ac.uk/pdbsum/4gxx 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=4gxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gxx OCA], [http://pdbe.org/4gxx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gxx RCSB], [http://www.ebi.ac.uk/pdbsum/4gxx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gxx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4gxx" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: I18a0]]
 [[Category: Ekiert, D C]]
 [[Category: Wilson, I A]]

4gxx

From Proteopedia

Revision as of 19:25, 4 August 2016

Crystal structure of the "avianized" 1918 influenza virus hemagglutinin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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