Biophysics Unit (CSIC-UPV/EHU) and Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), Bilbao, Spain.
PLoS One. 2012;7(12):e52740. doi: 10.1371/journal.pone.0052740. Epub 2012 Dec 21.
The membrane proximal external region (MPER) of the fusogenic HIV-1 glycoprotein-41 harbors the epitope sequence recognized by 2F5, a broadly neutralizing antibody isolated from an infected individual. Structural mimicry of the conserved MPER 2F5 epitope constitutes a pursued goal in the field of anti-HIV vaccine development. It has been proposed that 2F5 epitope folding into its native state is attained in the vicinity of the membrane interface and might involve interactions with other viral structures. Here we present results indicating that oligomeric complexes established between MPER and the conserved amino-terminal fusion peptide (FP) can partition into lipid vesicles and be specifically bound by the 2F5 antibody at their surfaces. Cryo-transmission electron microscopy of liposomes doped with MPER:FP peptide mixtures provided the structural grounds for complex recognition by antibody at lipid bilayer surfaces. Supporting the immunogenicity of the membrane-bound complex, these MPER:FP peptide-vesicle formulations could trigger cross-reactive anti-MPER antibodies in rabbits. Thus, our observations suggest that contacts with N-terminal regions of gp41 may stabilize the 2F5 epitope as a membrane-surface antigen.
融合蛋白 HIV-1 糖蛋白 41 的膜近端外部区域 (MPER) 含有 2F5 识别的表位序列，2F5 是从受感染个体中分离出的一种广泛中和抗体。结构模拟保守的 MPER 2F5 表位是抗 HIV 疫苗开发领域的一个追求目标。有人提出，2F5 表位折叠成其天然状态是在膜界面附近实现的，并且可能涉及与其他病毒结构的相互作用。在这里，我们提供的结果表明，MPER 和保守的氨基末端融合肽 (FP) 之间建立的寡聚复合物可以分配到脂质体中，并在其表面被 2F5 抗体特异性结合。用 MPER:FP 肽混合物掺杂的脂质体的冷冻传输电子显微镜为在脂质双层表面由抗体识别复合物提供了结构基础。支持膜结合复合物的免疫原性，这些 MPER:FP 肽 - 囊泡配方可以在兔子中引发交叉反应性抗 MPER 抗体。因此，我们的观察结果表明，与 gp41 的 N 端区域的接触可能稳定 2F5 表位作为膜表面抗原。
