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-Structure paper
| タイトル | Acquisition of quaternary trimer interaction as a key step in the lineage maturation of a broad and potent HIV-1 neutralizing antibody. |
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| ジャーナル・号・ページ | Structure, Vol. 33, Issue 8, Page 1325-11336.e5, Year 2025 |
| 掲載日 | 2025年8月7日 |
著者 | Qingbo Liu / Ruth J Parsons / Kevin Wiehe / Robert J Edwards / Kevin O Saunders / Peng Zhang / Huiyi Miao / Kedamawit Tilahun / Julia Jones / Yue Chen / Bhavna Hora / Wilton B Williams / David Easterhoff / Xiao Huang / Katarzyna Janowska / Katayoun Mansouri / Barton F Haynes / Priyamvada Acharya / Paolo Lusso / ![]() |
| PubMed 要旨 | Although most broadly neutralizing antibodies (bNAbs) specific for the CD4-binding site (CD4-BS) of HIV-1 interact with a single gp120 protomer, a few mimic the quaternary binding mode of CD4, making ...Although most broadly neutralizing antibodies (bNAbs) specific for the CD4-binding site (CD4-BS) of HIV-1 interact with a single gp120 protomer, a few mimic the quaternary binding mode of CD4, making contact with a second protomer through elongated heavy chain framework 3 (FRH3) or complementarity-determining region 1 (CDRH1) loops. Here, we show that a CDRH3-dominated anti-CD4-BS bNAb, CH103, establishes quaternary interaction despite regular-length FRH3 and CDRH1. This quaternary interaction is critical for neutralization and is primarily mediated by two FRH3 acidic residues that were sequentially acquired and subjected to strong positive selection during CH103 maturation. Cryoelectron microscopy (cryo-EM) structures confirmed the role of the two FRH3 acidic residues in mediating quaternary contact and demonstrated that CH103 reaches the adjacent gp120 protomer by virtue of its unique angle of approach. Thus, the acquisition of quaternary interaction may constitute a key step in the lineage maturation of a broad and potent HIV-1 neutralizing antibody. |
リンク | Structure / PubMed:40412376 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.37 - 13.0 Å |
| 構造データ | ![]() EMDB-44736: HIV Envelope trimer BG505 SOSIP.664 in complex with wild type CH103 antibody ![]() EMDB-44738: HIV Envelope BG505 SOSIP.664 in complex with one Fab of CH103 E75K/D76N mutant ![]() EMDB-44739: HIV Envelope trimer CH505 SOSIP.664 in complex with wild type CH103 antibody ![]() EMDB-44740: HIV Envelope trimer CH505 SOSIP.664 in complex with three CH103 E75K/D76N mutant antibody Fabs EMDB-46604, PDB-9d7g: EMDB-46605, PDB-9d7h: EMDB-46606, PDB-9d7i: EMDB-46613, PDB-9d7o: EMDB-46614, PDB-9d7p: |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | VIRAL PROTEIN / Trimer / Env / BG505 / CH103 / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex |
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Human immunodeficiency virus 2 (ヒト免疫不全ウイルス)
homo sapiens (ヒト)
human immunodeficiency virus 1 (ヒト免疫不全ウイルス)
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