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-Structure paper
タイトル | HIV-1 CD4-binding site germline antibody-Env structures inform vaccine design. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 6123, Year 2022 |
掲載日 | 2022年10月17日 |
著者 | Kim-Marie A Dam / Christopher O Barnes / Harry B Gristick / Till Schoofs / Priyanthi N P Gnanapragasam / Michel C Nussenzweig / Pamela J Bjorkman / |
PubMed 要旨 | BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4- ...BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs. To understand how SHMs correlate with BG24 neutralization of HIV-1, we report 4.1 Å and 3.4 Å single-particle cryo-EM structures of two inferred germline (iGL) BG24 precursors complexed with engineered Env-based immunogens lacking CD4bs N-glycans. Structures reveal critical Env contacts by BG24 and identify antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24 variants bound to Envs with CD4bs glycans present provide insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276 glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design. |
リンク | Nat Commun / PubMed:36253376 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.4 - 6.4 Å |
構造データ | EMDB-26490, PDB-7ugn: EMDB-26491: Cryo-EM structure of BG24 inferred germline Fabs with germline CDR3s and 10-1074 Fabs in complex with HIV-1 Env immunogen BG505-SOSIPv4.1-GT1 - Class 2 EMDB-26492, PDB-7ugo: EMDB-26493, PDB-7ugp: EMDB-26494: Cryo-EM map of BG24 Fabs with an inferred germline light chain and 10-1074 Fabs in complex with HIV-1 Env immunogen BG505-SOSIPv4.1-GT1 containing the N276 gp120 glycan- Class 2 EMDB-26495: Cryo-EM map of BG24 Fabs with an inferred germline light chain and 10-1074 Fabs in complex with HIV-1 Env immunogen BG505-SOSIPv4.1-GT1 containing the N276 gp120 glycan- Class 3 EMDB-26496, PDB-7ugq: PDB-7ugm: |
化合物 | ChemComp-HOH: ChemComp-NAG: ChemComp-MAN: |
由来 |
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キーワード | IMMUNE SYSTEM / Fab / IgG / BG24 / anti-HIV antibody / bNAb / VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Env / neutralizing antibody / CD4 binding site antibody / VIRAL PROTEIN / Germline / precursor / immunogen / VIRAL PROTEIN-IMMUNE SYSTEM complex |