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-Structure paper
タイトル | Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike. |
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ジャーナル・号・ページ | Nat Commun, Vol. 6, Page 8167, Year 2015 |
掲載日 | 2015年9月25日 |
著者 | Jeong Hyun Lee / Daniel P Leaman / Arthur S Kim / Alba Torrents de la Peña / Kwinten Sliepen / Anila Yasmeen / Ronald Derking / Alejandra Ramos / Steven W de Taeye / Gabriel Ozorowski / Florian Klein / Dennis R Burton / Michel C Nussenzweig / Pascal Poignard / John P Moore / Per Johan Klasse / Rogier W Sanders / Michael B Zwick / Ian A Wilson / Andrew B Ward / |
PubMed 要旨 | The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120-gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. ...The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120-gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 Å resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120-gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes. |
リンク | Nat Commun / PubMed:26404402 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.887 - 9.3 Å |
構造データ | EMDB-3067: PDB-5awn: PDB-5cck: |
化合物 | ChemComp-HOH: ChemComp-CXS: |
由来 |
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キーワード | IMMUNE SYSTEM / HIV-1 / Env / broadly neutralizing antibody / bnAb / antibody |