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-Structure paper
タイトル | Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core. |
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ジャーナル・号・ページ | Elife, Vol. 7, Year 2018 |
掲載日 | 2018年11月7日 |
著者 | Andrew J Borst / Connor E Weidle / Matthew D Gray / Brandon Frenz / Joost Snijder / M Gordon Joyce / Ivelin S Georgiev / Guillaume Be Stewart-Jones / Peter D Kwong / Andrew T McGuire / Frank DiMaio / Leonidas Stamatatos / Marie Pancera / David Veesler / |
PubMed 要旨 | VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding ...VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding VRC01 germline precursors poorly bind to Env. Immunogen design has mostly relied on glycan removal from trimeric Env constructs and has had limited success in eliciting mature VRC01 bnAbs. To better understand elicitation of such bnAbs, we characterized the inferred germline precursor of VRC01 in complex with a modified trimeric 426c Env by cryo-electron microscopy and a 426c gp120 core by X-ray crystallography, biolayer interferometry, immunoprecipitation, and glycoproteomics. Our results show VRC01 germline antibodies interacted with a wild-type 426c core lacking variable loops 1-3 in the presence and absence of a glycan at position Asn276, with the latter form binding with higher affinity than the former. Interactions in the presence of an Asn276 oligosaccharide could be enhanced upon carbohydrate shortening, which should be considered for immunogen design. |
リンク | Elife / PubMed:30403372 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.315 - 4.8 Å |
構造データ | EMDB-9294, PDB-6myy: EMDB-9295: EMDB-9303, PDB-6mzj: EMDB-9304: PDB-6mft: |
化合物 | ChemComp-NAG: ChemComp-PEG: ChemComp-CIT: ChemComp-EDO: ChemComp-HOH: |
由来 |
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キーワード | IMMUNE SYSTEM/VIRAL PROTEIN / glycans / germline / IMMUNE SYSTEM-VIRAL PROTEIN complex / VIRAL PROTEIN/IMMUNE SYSTEM / HIV envelope / germline VRC01 antibody / viral fusion protein / glycan shield / VIRAL PROTEIN-IMMUNE SYSTEM complex |