Acidic pH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike
Lassa virus is an enveloped, bi-segmented RNA virus and the most prevalent and fatal of all Old World arenaviruses. Virus entry into the host cell is mediated by a tripartite surface spike complex, which is composed of two viral glycoprotein subunits, GP1 and GP2, and the stable signal peptide. Of these, GP1 binds to cellular receptors and GP2 catalyzes fusion between the viral envelope and the host cell membrane during endocytosis. The molecular structure of the spike and conformational rearrangements induced by low pH, prior to fusion, remain poorly understood. Here, we analyzed the three-dimensional ultrastructure of Lassa virus using electron cryotomography. Sub-tomogram averaging yielded a structure of the glycoprotein spike at 14-Å resolution. The spikes are trimeric, cover the virion envelope, and connect to the underlying matrix. Structural changes to the spike, following acidification, support a viral entry mechanism dependent on binding to the lysosome-resident receptor LAMP1 and further dissociation of the membrane-distal GP1 subunits.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
PLoS pathogens - 12(2016), 2 vom: 08. Feb., Seite e1005418 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Sai [VerfasserIn] |
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| Links: |
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| Themen: |
Glycoproteins |
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| Anmerkungen: |
Date Completed 30.06.2016 Date Revised 13.12.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.ppat.1005418 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM257207996 |
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| 520 | |a Lassa virus is an enveloped, bi-segmented RNA virus and the most prevalent and fatal of all Old World arenaviruses. Virus entry into the host cell is mediated by a tripartite surface spike complex, which is composed of two viral glycoprotein subunits, GP1 and GP2, and the stable signal peptide. Of these, GP1 binds to cellular receptors and GP2 catalyzes fusion between the viral envelope and the host cell membrane during endocytosis. The molecular structure of the spike and conformational rearrangements induced by low pH, prior to fusion, remain poorly understood. Here, we analyzed the three-dimensional ultrastructure of Lassa virus using electron cryotomography. Sub-tomogram averaging yielded a structure of the glycoprotein spike at 14-Å resolution. The spikes are trimeric, cover the virion envelope, and connect to the underlying matrix. Structural changes to the spike, following acidification, support a viral entry mechanism dependent on binding to the lysosome-resident receptor LAMP1 and further dissociation of the membrane-distal GP1 subunits | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Glycoproteins |2 NLM | |
| 650 | 7 | |a LAMP1 protein, human |2 NLM | |
| 650 | 7 | |a Lysosomal Membrane Proteins |2 NLM | |
| 650 | 7 | |a Multiprotein Complexes |2 NLM | |
| 650 | 7 | |a Protein Sorting Signals |2 NLM | |
| 650 | 7 | |a Viral Envelope Proteins |2 NLM | |
| 700 | 1 | |a Sun, Zhaoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Pryce, Rhys |e verfasserin |4 aut | |
| 700 | 1 | |a Parsy, Marie-Laure |e verfasserin |4 aut | |
| 700 | 1 | |a Fehling, Sarah K |e verfasserin |4 aut | |
| 700 | 1 | |a Schlie, Katrin |e verfasserin |4 aut | |
| 700 | 1 | |a Siebert, C Alistair |e verfasserin |4 aut | |
| 700 | 1 | |a Garten, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a Bowden, Thomas A |e verfasserin |4 aut | |
| 700 | 1 | |a Strecker, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Huiskonen, Juha T |e verfasserin |4 aut | |
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