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GP1 of Lassa Virus
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==Importance== | ==Importance== | ||
<scene name='76/761695/5vk2on4zjf_histriad/4'>TextToBeDisplayed</scene> | <scene name='76/761695/5vk2on4zjf_histriad/4'>TextToBeDisplayed</scene> | ||
| - | Lassa virus (LASV), an Old World [https://en.wikipedia.org/wiki/Arenavirus arenavirus], is a notorious disease-causing agent primarily in West Africa that is able to spread to rodents, as well as humans. This deadly pathogen causes severe viral hemorrhagic fevers and significant mortality. So far, there are no available vaccines for LASV or any other viruses found in the ''Arenaviridae'' family. Determining the structure of the complete trimeric glycoprotein complex, composed of GP1, GP2, and SSP (stable signal peptide), will lay the foundation for a future discovery of novel antiviral drugs. This is the first representative structure for Old World arenaviruses. | + | Lassa virus (LASV), an Old World [https://en.wikipedia.org/wiki/Arenavirus arenavirus], is a notorious disease-causing agent primarily in West Africa that is able to spread to rodents, as well as humans. This deadly pathogen causes severe viral hemorrhagic fevers and significant mortality. So far, there are no available vaccines for LASV or any other viruses found in the ''Arenaviridae'' family. Determining the structure of the complete trimeric glycoprotein complex (GPC), composed of GP1, GP2, and SSP (stable signal peptide), will lay the foundation for a future discovery of novel antiviral drugs. This is the first representative structure for Old World arenaviruses. |
== Function == | == Function == | ||
'''GP1''' (Glycoprotein 1) is the receptor binding domain of LASV that mediates receptor recognition. Research thus far indicates that GP1 from LASV may undergo irreversible conformational changes that could serve as an immunological decoy mechanism. | '''GP1''' (Glycoprotein 1) is the receptor binding domain of LASV that mediates receptor recognition. Research thus far indicates that GP1 from LASV may undergo irreversible conformational changes that could serve as an immunological decoy mechanism. | ||
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GP1 of LASV is a 4 chain structure with <scene name='76/761695/Nag/1'>NAG</scene> ligands attached to each chain. The overall architecture of GP1 features a central β-sheet and two distinct halves: a glycosylated half containing the receptor-binding site that is made mostly by the central β-sheet and surrounding loops and a half that contains mostly helices and most likely faces the trimer axis<ref name="MolMechforLAMP1">DOI 10.1128/JVI.00651-15</ref>. The method used to determine this structure was [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray diffraction] | GP1 of LASV is a 4 chain structure with <scene name='76/761695/Nag/1'>NAG</scene> ligands attached to each chain. The overall architecture of GP1 features a central β-sheet and two distinct halves: a glycosylated half containing the receptor-binding site that is made mostly by the central β-sheet and surrounding loops and a half that contains mostly helices and most likely faces the trimer axis<ref name="MolMechforLAMP1">DOI 10.1128/JVI.00651-15</ref>. The method used to determine this structure was [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray diffraction] | ||
=== Histidine Triad=== | === Histidine Triad=== | ||
| - | Attached to this structure is a unique <scene name='76/761695/Histriad/5'>triad of histidines</scene> that is highly conserved among Old World arenaviruses. Located on the β-sheet face of GP1, the histidine triad is a structural element that directly interacts with [[LAMP1]] (Lysosome-associated membrane glycoprotein) and helps stabilize a LAMP1-"compatible" conformation by providing a molecular mechanism for the pH-dependent receptor switching<ref name="MolMechforLAMP1" />. The histidine triad is critical in forming a binding site for LAMP1 | + | Attached to this structure is a unique <scene name='76/761695/Histriad/5'>triad of histidines</scene> that is highly conserved among Old World arenaviruses. Located on the β-sheet face of GP1, the histidine triad is a structural element that directly interacts with [[LAMP1]] (Lysosome-associated membrane glycoprotein) and helps stabilize a LAMP1-"compatible" conformation by providing a molecular mechanism for the pH-dependent receptor switching<ref name="MolMechforLAMP1" />. The histidine triad is critical in forming a <scene name='76/761695/Lamp1bindingsite/1'>binding site for LAMP1. </scene> |
===LAMP1 Binding Site=== | ===LAMP1 Binding Site=== | ||
| - | The primary cellular receptor of LASV | + | The primary cellular receptor of LASV α-dystroglycan (α-DG), which is recognized by a trimeric class 1 viral GPC on the surface of the virus. Following successful attachment to α-DG on cells, LASV is internalized via macropinocytosis, and the GPC facilitates membrane fusion at the acidic environment of a late endosomal compartment. Recent studies have shown that successful infection by LASV requires it to switch in a pH-dependent manner from α-DG to LAMP1. |
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<scene name='76/761695/4zjf_chaina_hisandlampsite/1'>LAMP1 Binding sites with Histidine Triad</scene> | <scene name='76/761695/4zjf_chaina_hisandlampsite/1'>LAMP1 Binding sites with Histidine Triad</scene> | ||
Revision as of 08:53, 29 June 2017
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References
- ↑ 1.0 1.1 Cohen-Dvashi H, Cohen N, Israeli H, Diskin R. Molecular mechanism for LAMP1 recognition by Lassa Virus. J Virol. 2015 May 13. pii: JVI.00651-15. PMID:25972533 doi:http://dx.doi.org/10.1128/JVI.00651-15
Categories: Cohen, N | Cohen-Dvashi, H | Diskin, R | Israeli, H | Arenavirus | Glycoprotein | Lassa | LASV | Receptor binding | Viral protein | 4zjf | GP1
