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-Structure paper
タイトル | Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies. |
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ジャーナル・号・ページ | Cell Rep, Vol. 42, Issue 5, Page 112524, Year 2023 |
掲載日 | 2023年5月30日 |
著者 | Hailee R Perrett / Philip J M Brouwer / Jonathan Hurtado / Maddy L Newby / Lin Liu / Helena Müller-Kräuter / Sarah Müller Aguirre / Judith A Burger / Joey H Bouhuijs / Grace Gibson / Terrence Messmer / John S Schieffelin / Aleksandar Antanasijevic / Geert-Jan Boons / Thomas Strecker / Max Crispin / Rogier W Sanders / Bryan Briney / Andrew B Ward / |
PubMed 要旨 | 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. ...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. |
リンク | Cell Rep / PubMed:37209096 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.13 - 3.81 Å |
構造データ | EMDB-28178, PDB-8ejd: EMDB-28179, PDB-8eje: EMDB-28180, PDB-8ejf: EMDB-28181, PDB-8ejg: EMDB-28182, PDB-8ejh: EMDB-28183, PDB-8eji: EMDB-28184, PDB-8ejj: |
化合物 | ChemComp-NAG: ChemComp-MAN: |
由来 |
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キーワード | VIRAL PROTEIN / glycoprotein complex / Lassa mammarenavirus / LASV / GPC / immune system / viral fusion protein / Lassa virus / lineage IV / Josiah / lineage II / NIG08-A41 / lineage V / Soromba-R / lineage VI / Togo/2016/7082 / 12.1F / 19.7E / VIRAL PROTEIN/IMMUNE SYSTEM / S370.7 / VIRAL PROTEIN-IMMUNE SYSTEM complex |