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-Structure paper
タイトル | Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 4515, Year 2022 |
掲載日 | 2022年8月3日 |
著者 | Jelle van Schooten / Elinaz Farokhi / Anna Schorcht / Tom L G M van den Kerkhof / Hongmei Gao / Patricia van der Woude / Judith A Burger / Tim G Rijkhold Meesters / Tom Bijl / Riham Ghalaiyini / Hannah L Turner / Jessica Dorning / Barbera D C van Schaik / Antoine H C van Kampen / Celia C Labranche / Robyn L Stanfield / Devin Sok / David C Montefiori / Dennis R Burton / Michael S Seaman / Gabriel Ozorowski / Ian A Wilson / Rogier W Sanders / Andrew B Ward / Marit J van Gils / |
PubMed 要旨 | A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope ...A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope glycoprotein is of interest because, unlike the better-known VH1-2-derived VRC01-class bNAbs, it does not require a rare short light chain complementarity-determining region 3 (CDRL3). Here, we describe three IOMA-class NAbs, ACS101-103, with up to 37% breadth, that share many characteristics with IOMA, including an average-length CDRL3. Cryo-electron microscopy revealed that ACS101 shares interactions with those observed with other VH1-2 and VH1-46-class bNAbs, but exhibits a unique binding mode to residues in loop D. Analysis of longitudinal sequences from the patient suggests that a transmitter/founder-virus lacking the N276 glycan might have initiated the development of these NAbs. Together these data strengthen the rationale for germline-targeting vaccination strategies to induce IOMA-class bNAbs and provide a wealth of sequence and structural information to support such strategies. |
リンク | Nat Commun / PubMed:35922441 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.73 - 25.0 Å |
構造データ | EMDB-14474, PDB-7z3a: EMDB-14475: AMC009 SOSIPv5.2 + ACS101 Fab EMDB-14476: AMC009 SOSIPv5.2 in complex with ACS102 Fab EMDB-14477: AMC009 SOSIPv5.2 in complex with ACS103 Fab EMDB-14478: AMC009 SOSIPv5.2 in complex with ACS124 Fab PDB-7u04: PDB-7u0k: |
化合物 | ChemComp-GOL: ChemComp-HOH: ChemComp-NHE: ChemComp-NAG: |
由来 |
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キーワード | IMMUNE SYSTEM (免疫系) / Antibody (抗体) / IOMA / HIV (ヒト免疫不全ウイルス) / STRUCTURAL PROTEIN (タンパク質) / VIRAL PROTEIN (ウイルスタンパク質) / HIV-1 / antibodies (抗体) / CD4-binding site / gp41-gp120 interface |