GP1 of Lassa Virus

Importance

Lassa virus, an Old World 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.

Function

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.

Structural Highlights

GP1 of Lassa virus is a 4 chain structure with 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^[1]. The method used to determine this structure was X-ray diffraction

Histidine Triad

Attached to this structure is a 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^[1].

LAMP1 Binding Site

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.

Protein structure accession number: 4ZJF

For more information on this protein structure visit the following sites: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT