7SGE
I53-50 nanoparticle core reconstructed from GPC-I53-50NP by focused refinement
Summary for 7SGE
| Entry DOI | 10.2210/pdb7sge/pdb |
| EMDB information | 25107 25108 25109 |
| Descriptor | Josiah GPCysR4-I53-50A - nanoparticle component, I53-50B component (2 entities in total) |
| Functional Keywords | glycoprotein, lassa, josiah, vaccine design, nanoparticle, protein design, viral protein |
| Biological source | synthetic construct More |
| Total number of polymer chains | 2 |
| Total formula weight | 92082.45 |
| Authors | Antanasijevic, A.,Brouwer, P.J.M.,Ward, A.B. (deposition date: 2021-10-05, release date: 2022-10-12, Last modification date: 2024-10-16) |
| 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 Cited by 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: 36400021DOI: 10.1016/j.chom.2022.10.018 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.67 Å) |
Structure validation
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