EMD-26859

Single-particle
5.7 Å
EMD-26859 Deposition: 05/05/2022
Map released: 10/05/2023
Last modified: 28/02/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-26859

Ligand-free Lassa GPC Trimer with C3 Symmetry

EMD-26859

Single-particle
5.7 Å
EMD-26859 Deposition: 05/05/2022
Map released: 10/05/2023
Last modified: 28/02/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Lassa virus Josiah
Sample: Lassa GPC trimer

Deposition Authors: Gorman J , Kwong PD
Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability.
PUBMED: 38177144
DOI: doi:10.1038/s41467-023-44534-y
ISSN: 2041-1723
Abstract:
Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV. Cryo-EM analyses reveal D5 to recognize a cleavage-dependent site-of-vulnerability at the trimer apex. The recognized site appears specific to GPC intermediates, with protomers lacking full cleavage between GP1 and GP2 subunits. Guinea pig immunizations with the prefusion-stabilized cleavage-intermediate LASV GPC, first as trimer and then as a nanoparticle, induce neutralizing responses, targeting multiple epitopes including that of D5; we identify a neutralizing antibody (GP23) from the immunized guinea pigs. Collectively, our findings define a prefusion-stabilized GPC trimer, reveal an apex-situated site-of-vulnerability, and demonstrate elicitation of LASV-neutralizing responses by a cleavage-intermediate LASV trimer.