在8月出版的《自然—結(jié)構(gòu)和分子生物學(xué)》期刊上,，研究人員報(bào)告了一種人類抗體和一種在艾滋病病毒1（HIV－1）表面發(fā)現(xiàn)的蛋白質(zhì)之間的相互作用,。這種人類抗體名為D5，它能識(shí)別控制HIV-1融入宿主細(xì)胞膜過(guò)程的蛋白質(zhì)的中間形態(tài),。
為了進(jìn)入宿主細(xì)胞,，某些病毒必須首先與目標(biāo)細(xì)胞表面黏合在一起，然后再融化目標(biāo)細(xì)胞的細(xì)胞膜,。在HIV-1中,，控制融合過(guò)程的蛋白質(zhì)被稱為gp41，它在細(xì)胞膜融化過(guò)程中必須發(fā)生一系列的結(jié)構(gòu)變化,。這揭露出分子上的一種“被保護(hù)區(qū)域”,，它是一個(gè)理想抗體目標(biāo)，因?yàn)樗鼈冃蛄械淖兓惶l繁,；即使對(duì)不同的HIV菌株來(lái)說(shuō),，抗體“看”它們都是一樣的。
Andrea Carfi和同事報(bào)告說(shuō),，人類抗體D5能識(shí)別gp41的中間結(jié)構(gòu),。弄清楚這些分子間的相互作用也許有助于科學(xué)家們開發(fā)出更有力的對(duì)付HIV-1的抗體和治療藥物,。因?yàn)槠渌《疽矔?huì)融化宿主的細(xì)胞膜，因此,，將融化蛋白質(zhì)的中間態(tài)作為靶標(biāo)有可能成為開發(fā)廣泛適用的藥物和疫苗的戰(zhàn)略,。
英文原文：
Structural basis for HIV-1 neutralization by a gp41 fusion intermediate- directed antibody
Elicitation of potent and broadly neutralizing antibodies is an important goal in designing an effective human immunodeficiency virus-1 (HIV-1) vaccine. The HIV-1 gp41 inner-core trimer represents a functionally and structurally conserved target for therapeutics. Here we report the 2.0-A-resolution crystal structure of the complex between the antigen-binding fragment of D5, an HIV-1 cross-neutralizing antibody, and 5-helix, a gp41 inner-core mimetic. Both binding and neutralization depend on residues in the D5 CDR H2 loop protruding into the conserved gp41 hydrophobic pocket, as well as a large pocket in D5 surrounding core gp41 residues. Kinetic analysis of D5 mutants with perturbed D5-gp41 interactions suggests that D5 persistence at the fusion intermediate is crucial for neutralization. Thus, our data validate the gp41 N-peptide trimer fusion intermediate as a target for neutralizing antibodies and provide a template for identification of more potent and broadly neutralizing molecules.
