8ejf | pdb_00008ejf
Structure of lineage V Lassa virus glycoprotein complex (strain Soromba-R)
Structural highlights
FunctionV9VG48_LASV Forms the virion spikes together with glycoprotein G2. The glycoprotein spike trimers are connected to the underlying matrix. Interacts with the host receptor. Mediates virus attachment to the host primary receptor alpha-dystroglycan DAG1 (alpha-DG) at the cell surface. This attachment induces virion internalization apparently through macropinocytosis. Following endocytosis, there is a pH-dependent switch from binding DAG1 to the host lysosomal receptor LAMP1. This latter binding triggers the dissociation of GP1, exposing the fusion subunit, GP2, such that fusion can occur. Down-modulates host DAG1.[HAMAP-Rule:MF_04084] Forms the virion spikes together with glycoprotein G1. The glycoprotein spike trimers are connected to the underlying matrix. Class I viral fusion protein that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversible conformational changes induced by acidification.[HAMAP-Rule:MF_04084] Functions as a cleaved signal peptide that is retained as the third component of the GP complex (GP-C). Helps to stabilize the spike complex in its native conformation. The SSP is required for efficient glycoprotein expression, post-translational maturation cleavage of G1 and G2, glycoprotein transport to the cell surface plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.[HAMAP-Rule:MF_04084] Publication Abstract from PubMedLassa 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. , PMID:37209096[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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