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 with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lassa_mammarenavirus Lassa mammarenavirus]. 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>
+<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='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='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>
@@ Line 30: / Line 30: @@
 [[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lassa mammarenavirus]]
+[[Category: Mammarenavirus lassaense]]
 [[Category: Hastie KM]]
 [[Category: Saphire EO]]

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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