Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Acta Crystallogr D Struct Biol. 2017 Oct 1;73(Pt 10):822-828. doi: 10.1107/S2059798317013353. Epub 2017 Sep 29.
The structural and biochemical characterization of broadly neutralizing anti-HIV-1 antibodies (bNAbs) has been essential in guiding the design of potential vaccines to prevent infection by HIV-1. While these studies have revealed critical mechanisms by which bNAbs recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env), they have been limited to the visualization of high-mannose glycan forms only, since heterogeneity introduced from the presence of complex glycans makes it difficult to obtain high-resolution structures. 3.5 and 3.9 Å resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation were solved, revealing a glycan shield of high-mannose and complex-type N-glycans that were used to define the complete epitopes of two bNAbs. Here, the refinement of the N-glycans in the crystal structures is discussed and comparisons are made with glycan densities in glycosylated Env structures derived by single-particle cryo-electron microscopy.
广泛中和抗 HIV-1 抗体（bNAb）的结构和生化特性研究对于指导设计预防 HIV-1 感染的潜在疫苗至关重要。虽然这些研究揭示了 bNAb 识别和/或适应三聚体包膜糖蛋白（Env）上 N-聚糖的关键机制，但由于复杂聚糖的存在引入的异质性使得难以获得高分辨率结构，这些研究仅限于高甘露糖聚糖形式的可视化。解决了具有完全加工和天然糖基化的 HIV-1 Env 三聚体的 3.5 和 3.9 Å 分辨率晶体结构，揭示了高甘露糖和复杂型 N-聚糖的聚糖屏蔽，这些聚糖被用来定义两种 bNAb 的完整表位。在这里，讨论了晶体结构中 N-聚糖的精修，并与单颗粒冷冻电子显微镜衍生的糖基化 Env 结构中的聚糖密度进行了比较。
