Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments.
Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments.
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接口的亲和力是在膜环境中运行的抗体的效力。
DOI：
10.1016/j.celrep.2020.108037
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发表时间：
2020-08-18
期刊：
影响因子：
8.8
通讯作者：
Nieva JL
中科院分区：
文献类型：
--
作者：
Rujas E;Insausti S;Leaman DP;Carravilla P;González-Resines S;Monceaux V;Sánchez-Eugenia R;García-Porras M;Iloro I;Zhang L;Elortza F;Julien JP;Saéz-Cirión A;Zwick MB;Eggeling C;Ojida A;Domene C;Caaveiro JMM;Nieva JL
膜界面相互作用对抗体识别膜包埋抗原的贡献目前尚不清楚。该报告证明了通过化学修饰膜附近但不直接参与识别表位的区域来优化这种类型的抗体。使用HIV-1抗体10 E8作为模型，在选定的位点引入线性和多环合成芳香族化合物。分子动力学模拟预测这些合成化合物与病毒脂质膜的有利相互作用，HIV-1糖蛋白Env的表位位于该膜上。用芳香族乙酰胺对10 E8进行化学修饰，有利于对天然抗原的生产性和特异性识别，部分地掩埋在病毒膜的拥挤环境中，导致其阻断病毒感染的能力急剧增加。这些观察结果支持通过位点选择性化学修饰来利用界面亲和力以优化靶向近膜表位的抗体的功能。Rujas等人描述了抗体的位点选择性化学修饰，以改善膜表面表位的分子识别。使用芳香族化合物的修饰显著增强了针对膜嵌入的MPER表位的HIV-1抗体的病毒中和效力和天然抗原结合效率。
The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognition of the epitope. Using the HIV-1 antibody 10E8 as a model, linear and polycyclic synthetic aromatic compounds are introduced at selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipid membrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemical modification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buried in the crowded environment of the viral membrane, resulting in a dramatic increase of its capacity to block viral infection. These observations support the harnessing of interfacial affinity through site-selective chemical modification to optimize the function of antibodies that target membrane-proximal epitopes. Rujas et al. describe the site-selective chemical modification of antibodies to improve the molecular recognition of epitopes at membrane surfaces. The modification using aromatic compounds dramatically enhanced the virus neutralization potency and native antigen binding efficiency of HIV-1 antibodies directed against the membrane-embedded MPER epitope.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
64.8
作者：
Huang J;Ofek G;Laub L;Louder MK;Doria-Rose NA;Longo NS;Imamichi H;Bailer RT;Chakrabarti B;Sharma SK;Alam SM;Wang T;Yang Y;Zhang B;Migueles SA;Wyatt R;Haynes BF;Kwong PD;Mascola JR;Connors M
通讯作者：
Connors M
超分辨率显微镜揭示了过氧化物酶体膜蛋白的分室化。
DOI：
10.1074/jbc.m116.734038
发表时间：
2016-08-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Galiani S;Waithe D;Reglinski K;Cruz-Zaragoza LD;Garcia E;Clausen MP;Schliebs W;Erdmann R;Eggeling C
通讯作者：
Eggeling C
影响因子：
21.8
作者：
Krall, Nikolaus;da Cruz, Filipa P.;Bernardes, Goncalo J. L.
通讯作者：
Bernardes, Goncalo J. L.
影响因子：
3.4
作者：
Hoff, B;Strandberg, E;Posten, C
通讯作者：
Posten, C