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首页> 外文期刊>Immunity >Crystallographic Identification of Lipid as an Integral Component of the Epitope of HIV Broadly Neutralizing Antibody 4E10
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Crystallographic Identification of Lipid as an Integral Component of the Epitope of HIV Broadly Neutralizing Antibody 4E10

机译：脂质的晶体学鉴定为HIV广泛中和抗体4E10的抗原决定簇的组成部分。

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Numerous studies of the anti-HIV-1 envelope glycoprotein 41 (gp41) broadly neutralizing antibody 4E10 suggest that 4E10 also interacts with membrane lipids, but the antibody regions contacting lipids and its orientation with respect to the viral membrane are unknown. Vaccine immunogens capable of re-eliciting these membrane proximal external region (MPER)-like antibodies may require a lipid component to be successful. We performed a systematic crystallographic study of lipid binding to 4E10 to identify lipids bound by the antibody and the lipid-interacting regions. We identified phosphatidic acid, phosphatidylglycerol, and glycerol phosphate as specific ligands for 4E10 in the crystal structures. 4E10 used its CDRH1 loop to bind the lipid head groups, while its CDRH3 interacted with the hydrophobic lipid tails. Identification of the lipid binding sites on 4E10 may aid design of immunogens for vaccines that include a lipid component in addition to the MPER on gp41 for generation of broadly neutralizing antibodies.
机译：大量中和抗体4E10的抗HIV-1包膜糖蛋白41（gp41）的大量研究表明4E10也与膜脂质相互作用，但是与脂质接触的抗体区域及其相对于病毒膜的方向尚不清楚。能够重新引发这些膜近端外部区域（MPER）样抗体的疫苗免疫原可能需要脂质成分才能成功。我们对脂质与4E10的结合进行了系统的晶体学研究，以鉴定与抗体和脂质相互作用区域结合的脂质。我们确定磷脂酸，磷脂酰甘油和磷酸甘油为晶体结构中4E10的特定配体。 4E10使用其CDRH1环结合脂质头基，而其CDRH3与疏水性脂质尾巴相互作用。鉴定4E10上的脂质结合位点可有助于设计疫苗的免疫原，该疫苗除gp41上的MPER外还包括脂质成分，用于产生广泛中和的抗体。

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