7qu1

From Proteopedia

(Difference between revisions)

Current revision

Machupo virus GP1 glycoprotein in complex with Fab fragment of antibody MAC1

Structural highlights

7qu1 is a 3 chain structure with sequence from Mammarenavirus machupoense and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.91Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q6PXP4_MACHU Forms the virion spikes together with glycoprotein G2. The glycoprotein spike trimers are connected to the underlying matrix. Interacts with the host receptor leading to virus endocytosis.[HAMAP-Rule:MF_04084] Forms the virion spikes together with glycoprotein G1. The glycoprotein spike trimers are connected to the underlying matrix. 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 by acidification.[HAMAP-Rule:MF_04084] Functions as a cleaved signal peptide that is retained as the third component of the GP complex (GP-C). Helps to stabilize the spike complex in its native conformation. The SSP is required for efficient glycoprotein expression, post-translational maturation cleavage of G1 and G2, 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]

Publication Abstract from PubMed

Transmission of the New World hemorrhagic fever arenaviruses Junin virus (JUNV) and Machupo virus (MACV) to humans is facilitated, in part, by the interaction between the arenavirus GP1 glycoprotein and the human transferrin receptor 1 (hTfR1). We utilize a mouse model of live-attenuated immunization with envelope exchange viruses to isolate neutralizing monoclonal antibodies (NAbs) specific to JUNV GP1 and MACV GP1. Structures of two NAbs, termed JUN1 and MAC1, demonstrate that they neutralize through disruption of hTfR1 recognition. JUN1 utilizes a binding mode common to all characterized infection- and vaccine-elicited JUNV-specific NAbs, which involves mimicking hTfR1 binding through the insertion of a tyrosine into the receptor-binding site. In contrast, MAC1 undergoes a tyrosine-mediated mode of antigen recognition distinct from that used by the reported anti-JUNV NAbs and the only other characterized anti-MACV NAb. These data reveal the varied modes of GP1-specific recognition among New World arenaviruses by the antibody-mediated immune response. IMPORTANCE The GP1 subcomponent of the New World arenavirus GP is a primary target of the neutralizing antibody response, which has been shown to be effective in the prevention and treatment of infection. Here, we characterize the structural basis of the antibody-mediated immune response that arises from immunization of mice against Junin virus and Machupo virus, two rodent-borne zoonotic New World arenaviruses. We isolate a panel of GP1-specific monoclonal antibodies that recognize overlapping epitopes and exhibit neutralizing behavior, in vitro. Structural characterization of two of these antibodies indicates that antibody recognition likely interferes with GP1-mediated recognition of the transferrin receptor 1. These data provide molecular-level detail for a key region of vulnerability on the New World arenavirus surface and a blueprint for therapeutic antibody development.

Contrasting Modes of New World Arenavirus Neutralization by Immunization-Elicited Monoclonal Antibodies.,Ng WM, Sahin M, Krumm SA, Seow J, Zeltina A, Harlos K, Paesen GC, Pinschewer DD, Doores KJ, Bowden TA mBio. 2022 Apr 26;13(2):e0265021. doi: 10.1128/mbio.02650-21. Epub 2022 Mar 22. PMID:35315691^[1]

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

References

↑ Ng WM, Sahin M, Krumm SA, Seow J, Zeltina A, Harlos K, Paesen GC, Pinschewer DD, Doores KJ, Bowden TA. Contrasting Modes of New World Arenavirus Neutralization by Immunization-Elicited Monoclonal Antibodies. mBio. 2022 Apr 26;13(2):e0265021. PMID:35315691 doi:10.1128/mbio.02650-21

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/7qu1"

@@ Line 3: / Line 3: @@
 <StructureSection load='7qu1' size='340' side='right'caption='[[7qu1]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7qu1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Machupo_mammarenavirus Machupo mammarenavirus] 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=7QU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QU1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7qu1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mammarenavirus_machupoense Mammarenavirus machupoense] 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=7QU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QU1 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]] 1.91&#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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Machupo mammarenavirus]]
+[[Category: Mammarenavirus machupoense]]
 [[Category: Mus musculus]]
 [[Category: Bowden TA]]

7qu1

From Proteopedia

Current revision

Machupo virus GP1 glycoprotein in complex with Fab fragment of antibody MAC1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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