Biophysics Unit (CSIC-UPV/EHU) and Biochemistry Department, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.
J Mol Recognit. 2011 Jul-Aug;24(4):642-6. doi: 10.1002/jmr.1092.
The conserved membrane proximal external region (MPER), adjacent to the transmembrane domain (TMD) of human immunodeficiency virus type-1 (HIV-1) gp41 glycoprotein subunit, is accessible to the broadly neutralizing 4E10 and 2F5 monoclonal antibodies (mAbs) and, therefore, constitutes a potential target for vaccine design. This gp41 domain is postulated to be functional during the Env glycoprotein-mediated fusion reaction by destabilizing the highly rigid viral envelope. To perform this task, the aromatic-rich MPER is believed to insert into the interfacial region of the viral membrane external monolayer, thereby inducing the restructuring of the lipid bilayer required for fusion-pore opening. This model predicts that: (i) 2F5 and 4E10 mAbs are capable of binding epitopes inserted into the membrane interface; (ii) in-membrane binding will result in effective blocking of MPER membrane activity; and (iii) both processes, in-membrane recognition and blocking of membrane activity, can be modulated by altering both the lipid composition and the MPER amino acid sequence. We review here recently reported experimental data consistent with those predictions, and further speculate on their relevance for prospective anti-HIV vaccine development.
保守的膜近外部区域（MPER）紧邻人类免疫缺陷病毒 1 型（HIV-1）gp41 糖蛋白亚基的跨膜域（TMD），可被广泛中和的 4E10 和 2F5 单克隆抗体（mAb）识别，因此构成了疫苗设计的潜在靶标。该 gp41 结构域在 Env 糖蛋白介导的融合反应中被假定具有功能，通过破坏高度刚性的病毒包膜来使包膜不稳定。为了执行此任务，富含芳香族的 MPER 被认为插入病毒膜外单层的界面区域，从而诱导融合孔打开所需的脂质双层的重构。该模型预测：（i）2F5 和 4E10 mAb 能够结合插入到膜界面的表位；（ii）膜内结合将有效阻止 MPER 膜活性；（iii）通过改变脂质组成和 MPER 氨基酸序列，可以调节这两个过程，即膜内识别和阻断膜活性。我们在这里回顾了最近报道的与这些预测一致的实验数据，并进一步推测了它们对未来抗 HIV 疫苗开发的相关性。
