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-Structure paper
タイトル | An MPER antibody neutralizes HIV-1 using germline features shared among donors. |
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ジャーナル・号・ページ | Nat Commun, Vol. 10, Issue 1, Page 5389, Year 2019 |
掲載日 | 2019年11月26日 |
![]() | Lei Zhang / Adriana Irimia / Lingling He / Elise Landais / Kimmo Rantalainen / Daniel P Leaman / Thomas Vollbrecht / Armando Stano / Daniel I Sands / Arthur S Kim / / Pascal Poignard / Dennis R Burton / Ben Murrell / Andrew B Ward / Jiang Zhu / Ian A Wilson / Michael B Zwick / ![]() ![]() ![]() |
PubMed 要旨 | The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic ...The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 1.402 - 8.9 Å |
構造データ | ![]() EMDB-0620: ![]() PDB-6o3d: ![]() PDB-6o3g: ![]() PDB-6o3j: ![]() PDB-6o3k: ![]() PDB-6o3l: ![]() PDB-6o3u: ![]() PDB-6o41: ![]() PDB-6o42: |
化合物 | ![]() ChemComp-GOL: ![]() ChemComp-SO4: ![]() ChemComp-HOH: ![]() ChemComp-44E: ![]() ChemComp-MPD: ![]() ChemComp-PO4: |
由来 |
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![]() | IMMUNE SYSTEM / PGZL1 ANTI HIV-1 / GP41 MPER / MEMBRANE LIPIDS / BROADLY NEUTRALISING HIV-1 ANTIBODY / PGZL1.H4K3 ANTI HIV-1 / germline PGZL1 ANTI HIV-1 |