A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield.
A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield.
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DOI：
10.1126/science.1213256
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发表时间：
2011-11-25
期刊：
影响因子：
--
通讯作者：
Wilson IA
中科院分区：
文献类型：
--
作者：
Pejchal R;Doores KJ;Walker LM;Khayat R;Huang PS;Wang SK;Stanfield RL;Julien JP;Ramos A;Crispin M;Depetris R;Katpally U;Marozsan A;Cupo A;Maloveste S;Liu Y;McBride R;Ito Y;Sanders RW;Ogohara C;Paulson JC;Feizi T;Scanlan CN;Wong CH;Moore JP;Olson WC;Ward AB;Poignard P;Schief WR;Burton DR;Wilson IA
HIV包膜（Env）蛋白gp120通过密集的聚糖屏障保护免受抗体识别。然而，最近鉴定的几种PGT广泛中和抗体似乎与HIV聚糖外壳直接相互作用。分别在1.65和1.29 nm分辨率下具有Man9的Fab PGT 127和128的晶体结构和聚糖结合数据描绘了特异性高甘露糖结合位点。Fab PGT128与完全糖基化的gp120外结构域在3.25 nm处复合，揭示抗体穿透聚糖屏蔽并识别两个保守聚糖以及gp120 V3环的短β链片段，这是其高结合亲和力和广泛特异性的原因。此外，我们的数据表明，PGT127和128 IgG的高中和效力可能是由病毒表面上的交联Env三聚体介导的。
The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of Fabs PGT 127 and 128 with Man9 at 1.65 and 1.29 Å resolution, respectively, and glycan binding data delineate a specific high mannose binding site. Fab PGT 128 complexed with a fully-glycosylated gp120 outer domain at 3.25 Å reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short β-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificify. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 IgGs may be mediated by cross-linking Env trimers on the viral surface.
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