7SGD

Lassa virus glycoprotein construct(Josiah GPCysR4) recovered from GPC-I53-50 nanoparticle by localized reconstruction

Summary for 7SGD

• Entry DOI: 10.2210/pdb7sgd/pdb
• EMDB information: 25107 25108 25109
• Descriptor: Josiah GPCysR4 I53-50A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: glycoprotein, lassa, josiah, vaccine design, nanoparticle, protein design, viral protein
• Biological source: Lassa mammarenavirus; More
• Total number of polymer chains: 6
• Total formula weight: 458243.61

Authors

Antanasijevic, A.,Brouwer, P.J.M.,Ward, A.B. (deposition date: 2021-10-05, release date: 2022-10-12, Last modification date: 2024-10-09)

Primary citation

Brouwer, P.J.M.,Antanasijevic, A.,Ronk, A.J.,Muller-Krauter, H.,Watanabe, Y.,Claireaux, M.,Perrett, H.R.,Bijl, T.P.L.,Grobben, M.,Umotoy, J.C.,Schriek, A.I.,Burger, J.A.,Tejjani, K.,Lloyd, N.M.,Steijaert, T.H.,van Haaren, M.M.,Sliepen, K.,de Taeye, S.W.,van Gils, M.J.,Crispin, M.,Strecker, T.,Bukreyev, A.,Ward, A.B.,Sanders, R.W.
Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.
Cell Host Microbe, 30:1759-, 2022

PubMed Abstract: The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation. These GPC nanoparticles present twenty prefusion GPC trimers on the surface of an icosahedral particle. Cryo-EM studies of GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against the lethal Lassa virus challenge in guinea pigs. Additionally, we isolated a neutralizing antibody that mapped to the putative receptor-binding site, revealing a previously undefined site of vulnerability. Collectively, these findings offer potential approaches to vaccine and therapeutic design for the Lassa virus.

PubMed: 36400021
DOI: 10.1016/j.chom.2022.10.018

Experimental method

ELECTRON MICROSCOPY (3.97 Å)