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GP1 of Lassa Virus

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<StructureSection load='4zjf' size='340' side='right' caption='4ZJF structure' scene=''>
<StructureSection load='4zjf' size='340' side='right' caption='4ZJF structure' scene=''>
==Importance==
==Importance==
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Lassa virus, 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 Lassa virus 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.
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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.
== Function ==
== Function ==
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'''GP1''' (Glycoprotein 1) is the receptor binding domain of Lassa virus that mediates receptor recognition. Research thus far indicates that GP1 from Lassa virus may undergo irreversible conformational changes that could serve as an immunological decoy mechanism.
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'''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.
==Structural Highlights==
==Structural Highlights==
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GP1 of Lassa virus is a 4 chain structure with <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>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
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GP1 of LASV is a 4 chain structure with <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>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]
[https://en.wikipedia.org/wiki/X-ray_crystallography X-ray diffraction]
=== Histidine Triad===
=== Histidine Triad===
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Attached to this structure is a <scene name='76/761695/Histriad/5'>unique 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]] and helps stabilize a LAMP1-"compatible" conformation by providing a molecular mechanism for the pH-dependent receptor switching<ref name="MolMechforLAMP1" />.
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Attached to this structure is a <scene name='76/761695/Histriad/5'>unique 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]] and helps stabilize a LAMP1-"compatible" conformation by providing a molecular mechanism for the pH-dependent receptor switching<ref name="MolMechforLAMP1" />. The binding of LAMP1 triggers the glycoprotein spike complex of
===LAMP1 Binding Site===
===LAMP1 Binding Site===
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Recent studies show that receptor switching is critical during cell entry of Lassa virus. Receptor switching to LAMP1 is critical for triggering membrane fusion by Lassa virus.
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Recent studies show that receptor switching is critical during cell entry of LASV. Receptor switching to LAMP1 is critical for triggering membrane fusion by LASV.
Protein structure accession number: '''4ZJF'''
Protein structure accession number: '''4ZJF'''
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[[Category: Glycoprotein]]
[[Category: Glycoprotein]]
[[Category: Lassa]]
[[Category: Lassa]]
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[[Category: LASV]]
[[Category: Receptor binding]]
[[Category: Receptor binding]]
[[Category: Viral protein]]
[[Category: Viral protein]]
[[Category: 4zjf]]
[[Category: 4zjf]]
[[Category: GP1]]
[[Category: GP1]]

Revision as of 07:35, 27 June 2017

4ZJF structure

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References

  1. ↑ 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

Proteopedia Page Contributors and Editors (what is this?)

Rebecca Holstein, Michal Harel

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