6p91

From Proteopedia

(Difference between revisions)

Current revision

Structure of Lassa virus glycoprotein bound to Fab 18.5C

Structural highlights

6p91 is a 4 chain structure with sequence from Homo sapiens and Mammarenavirus lassaense. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 4Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GLYC_LASSJ Stable signal peptide (SSP) is cleaved but is apparently retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational cleavage of GP1 and GP2, glycoprotein transport to the cell plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion. The GP complex interacts with host glycosylated LAMP1 to mediate efficient infection.^[1] Glycoprotein G1 mediates virus attachment to host receptor alpha-dystroglycan DAG1. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis. Glycoprotein G2 is a class I viral fusion protein, that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversable conformational changes induced upon acidification in the endosome (By similarity).

Publication Abstract from PubMed

Lassa virus (LASV) causes hemorrhagic fever and is endemic in West Africa. Protective antibody responses primarily target the LASV surface glycoprotein (GPC), and GPC-B competition group antibodies often show potent neutralizing activity in humans. However, which features confer potent and broadly neutralizing antibody responses is unclear. Here, we compared three crystal structures of LASV GPC complexed with GPC-B antibodies of varying neutralization potency. Each GPC-B antibody recognized an overlapping epitope involved in binding of two adjacent GPC monomers and preserved the prefusion trimeric conformation. Differences among GPC-antibody interactions highlighted specific residues that enhance neutralization. Using structure-guided amino acid substitutions, we increased the neutralization potency and breadth of these antibodies to include all major LASV lineages. The ability to define antibody residues that allow potent and broad neutralizing activity, together with findings from analyses of inferred germline precursors, is critical to develop potent therapeutics and for vaccine design and assessment.

Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization.,Hastie KM, Cross RW, Harkins SS, Zandonatti MA, Koval AP, Heinrich ML, Rowland MM, Robinson JE, Geisbert TW, Garry RF, Branco LM, Saphire EO Cell. 2019 Aug 8;178(4):1004-1015.e14. doi: 10.1016/j.cell.2019.07.020. PMID:31398326^[2]

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

References

↑ Jae LT, Raaben M, Herbert AS, Kuehne AI, Wirchnianski AS, Soh TK, Stubbs SH, Janssen H, Damme M, Saftig P, Whelan SP, Dye JM, Brummelkamp TR. Virus entry. Lassa virus entry requires a trigger-induced receptor switch. Science. 2014 Jun 27;344(6191):1506-10. doi: 10.1126/science.1252480. PMID:24970085 doi:http://dx.doi.org/10.1126/science.1252480
↑ Hastie KM, Cross RW, Harkins SS, Zandonatti MA, Koval AP, Heinrich ML, Rowland MM, Robinson JE, Geisbert TW, Garry RF, Branco LM, Saphire EO. Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization. Cell. 2019 Aug 8;178(4):1004-1015.e14. doi: 10.1016/j.cell.2019.07.020. PMID:31398326 doi:http://dx.doi.org/10.1016/j.cell.2019.07.020

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/6p91"

Categories: Homo sapiens | Large Structures | Mammarenavirus lassaense | Hastie KM | Saphire EO

@@ Line 3: / Line 3: @@
 <StructureSection load='6p91' size='340' side='right'caption='[[6p91]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6p91]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P91 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P91 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6p91]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mammarenavirus_lassaense Mammarenavirus lassaense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P91 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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4&#8491;</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=6p91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p91 OCA], [http://pdbe.org/6p91 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p91 RCSB], [http://www.ebi.ac.uk/pdbsum/6p91 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p91 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <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'>[https://proteopedia.org/fgij/fg.htm?mol=6p91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p91 OCA], [https://pdbe.org/6p91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p91 RCSB], [https://www.ebi.ac.uk/pdbsum/6p91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p91 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/Q6GWS0_9VIRU Q6GWS0_9VIRU]] Glycoprotein G1: interacts with the host receptor.[HAMAP-Rule:MF_04084]  Glycoprotein G2: class I viral fusion protein that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversible conformational changes induced upon acidification in the endosome.[HAMAP-Rule:MF_04084]  Stable signal peptide (SSP): cleaved and functions as a signal peptide. In addition, it is also retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational maturation cleavage of GP1 and GP2, glycoprotein transport to the cell surface plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.[HAMAP-Rule:MF_04084]
+[https://www.uniprot.org/uniprot/GLYC_LASSJ GLYC_LASSJ] Stable signal peptide (SSP) is cleaved but is apparently retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational cleavage of GP1 and GP2, glycoprotein transport to the cell plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion. The GP complex interacts with host glycosylated LAMP1 to mediate efficient infection.<ref>PMID:24970085</ref>   Glycoprotein G1 mediates virus attachment to host receptor alpha-dystroglycan DAG1. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis.  Glycoprotein G2 is a class I viral fusion protein, that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversable conformational changes induced upon acidification in the endosome (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 6p91" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[Glycoprotein GP 3D structures|Glycoprotein GP 3D structures]]
+*[[3D structures of human antibody|3D structures of human antibody]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Hastie, K M]]
+[[Category: Mammarenavirus lassaense]]
-[[Category: Saphire, E O]]
+[[Category: Hastie KM]]
-[[Category: Antibody]]
+[[Category: Saphire EO]]
-[[Category: Glycoprotein]]
-[[Category: Lassa virus]]
-[[Category: Viral protein]]
-[[Category: Viral protein-immune system complex]]

6p91

From Proteopedia

Current revision

Structure of Lassa virus glycoprotein bound to Fab 18.5C

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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