Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization
Transmission of hemorrhagic fever New World arenaviruses from their rodent reservoirs to human populations poses substantial public health and economic dangers. These zoonotic events are enabled by the specific interaction between the New World arenaviral attachment glycoprotein, GP1, and cell surface human transferrin receptor (hTfR1). Here, we present the structural basis for how a mouse-derived neutralizing antibody (nAb), OD01, disrupts this interaction by targeting the receptor-binding surface of the GP1 glycoprotein from Junín virus (JUNV), a hemorrhagic fever arenavirus endemic in central Argentina. Comparison of our structure with that of a previously reported nAb complex (JUNV GP1-GD01) reveals largely overlapping epitopes but highly distinct antibody-binding modes. Despite differences in GP1 recognition, we find that both antibodies present a key tyrosine residue, albeit on different chains, that inserts into a central pocket on JUNV GP1 and effectively mimics the contacts made by the host TfR1. These data provide a molecular-level description of how antibodies derived from different germline origins arrive at equivalent immunological solutions to virus neutralization.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:114 |
|---|---|
| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 114(2017), 27 vom: 03. Juli, Seite 7031-7036 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zeltina, Antra [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 12.06.2018 Date Revised 29.01.2022 published: Print-Electronic PDB: 5NUZ Citation Status MEDLINE |
|---|
| doi: |
10.1073/pnas.1702127114 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM273086251 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM273086251 | ||
| 003 | DE-627 | ||
| 005 | 20231225000338.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.1702127114 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0910.xml |
| 035 | |a (DE-627)NLM273086251 | ||
| 035 | |a (NLM)28630325 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zeltina, Antra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.06.2018 | ||
| 500 | |a Date Revised 29.01.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a PDB: 5NUZ | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Transmission of hemorrhagic fever New World arenaviruses from their rodent reservoirs to human populations poses substantial public health and economic dangers. These zoonotic events are enabled by the specific interaction between the New World arenaviral attachment glycoprotein, GP1, and cell surface human transferrin receptor (hTfR1). Here, we present the structural basis for how a mouse-derived neutralizing antibody (nAb), OD01, disrupts this interaction by targeting the receptor-binding surface of the GP1 glycoprotein from Junín virus (JUNV), a hemorrhagic fever arenavirus endemic in central Argentina. Comparison of our structure with that of a previously reported nAb complex (JUNV GP1-GD01) reveals largely overlapping epitopes but highly distinct antibody-binding modes. Despite differences in GP1 recognition, we find that both antibodies present a key tyrosine residue, albeit on different chains, that inserts into a central pocket on JUNV GP1 and effectively mimics the contacts made by the host TfR1. These data provide a molecular-level description of how antibodies derived from different germline origins arrive at equivalent immunological solutions to virus neutralization | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a antibody response | |
| 650 | 4 | |a arenavirus | |
| 650 | 4 | |a glycoprotein | |
| 650 | 4 | |a hemorrhagic fever | |
| 650 | 4 | |a structure | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Glycoproteins |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a Viral Envelope Proteins |2 NLM | |
| 700 | 1 | |a Krumm, Stefanie A |e verfasserin |4 aut | |
| 700 | 1 | |a Sahin, Mehmet |e verfasserin |4 aut | |
| 700 | 1 | |a Struwe, Weston B |e verfasserin |4 aut | |
| 700 | 1 | |a Harlos, Karl |e verfasserin |4 aut | |
| 700 | 1 | |a Nunberg, Jack H |e verfasserin |4 aut | |
| 700 | 1 | |a Crispin, Max |e verfasserin |4 aut | |
| 700 | 1 | |a Pinschewer, Daniel D |e verfasserin |4 aut | |
| 700 | 1 | |a Doores, Katie J |e verfasserin |4 aut | |
| 700 | 1 | |a Bowden, Thomas A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d 1915 |g 114(2017), 27 vom: 03. Juli, Seite 7031-7036 |w (DE-627)NLM000008982 |x 1091-6490 |7 nnns |
| 773 | 1 | 8 | |g volume:114 |g year:2017 |g number:27 |g day:03 |g month:07 |g pages:7031-7036 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.1702127114 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 114 |j 2017 |e 27 |b 03 |c 07 |h 7031-7036 | ||