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8EJD

Structure of lineage IV Lassa virus glycoprotein complex (strain Josiah)

Summary for 8EJD
Entry DOI10.2210/pdb8ejd/pdb
EMDB information28178
DescriptorGlycoprotein G1, Glycoprotein G2, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
Functional Keywordsglycoprotein complex, lassa mammarenavirus, lasv, gpc, immune system, viral fusion protein, lassa virus, lineage iv, josiah, viral protein
Biological sourceLassa mammarenavirus
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Total number of polymer chains6
Total formula weight238706.31
Authors
Perrett, H.R.,Ward, A.B. (deposition date: 2022-09-16, release date: 2023-06-07, Last modification date: 2024-05-01)
Primary citationPerrett, H.R.,Brouwer, P.J.M.,Hurtado, J.,Newby, M.L.,Liu, L.,Muller-Krauter, H.,Muller Aguirre, S.,Burger, J.A.,Bouhuijs, J.H.,Gibson, G.,Messmer, T.,Schieffelin, J.S.,Antanasijevic, A.,Boons, G.J.,Strecker, T.,Crispin, M.,Sanders, R.W.,Briney, B.,Ward, A.B.
Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies.
Cell Rep, 42:112524-112524, 2023
Cited by
PubMed Abstract: Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.
PubMed: 37209096
DOI: 10.1016/j.celrep.2023.112524
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.8 Å)
Structure validation

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