4ZJF

Crystal structure of GP1 - the receptor binding domain of Lassa virus

Summary for 4ZJF

• Entry DOI: 10.2210/pdb4zjf/pdb
• Descriptor: Glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: arenaviruse, lassa, receptor binding, glycoprotein, viral protein
• Biological source: Lassa virus Josiah
• Total number of polymer chains: 4
• Total formula weight: 81834.84

Authors

Cohen-Dvashi, H.,Cohen, N.,Israeli, H.,Diskin, R. (deposition date: 2015-04-29, release date: 2015-05-27, Last modification date: 2024-11-20)

Primary citation

Cohen-Dvashi, H.,Cohen, N.,Israeli, H.,Diskin, R.
Molecular Mechanism for LAMP1 Recognition by Lassa Virus.
J.Virol., 89:7584-7592, 2015

PubMed Abstract: Lassa virus is a notorious human pathogen that infects many thousands of people each year in West Africa, causing severe viral hemorrhagic fevers and significant mortality. The surface glycoprotein of Lassa virus mediates receptor recognition through its GP1 subunit. Here we report the crystal structure of GP1 from Lassa virus, which is the first representative GP1 structure for Old World arenaviruses. We identify a unique triad of histidines that forms a binding site for LAMP1, a known lysosomal protein recently discovered to be a critical receptor for internalized Lassa virus at acidic pH. We demonstrate that mutation of this histidine triad, which is highly conserved among Old World arenaviruses, impairs LAMP1 recognition. Our biochemical and structural data further suggest that GP1 from Lassa virus may undergo irreversible conformational changes that could serve as an immunological decoy mechanism. Together with a variable region that we identify on the surface of GP1, those could be two distinct mechanisms that Lassa virus utilizes to avoid antibody-based immune response.

PubMed: 25972533
DOI: 10.1128/JVI.00651-15

Experimental method

X-RAY DIFFRACTION (2.595 Å)