A MOLECULAR CLASP IN THE HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 TM PROTEIN DETERMINES THE ANTI-HIV ACTIVITY OF GP41 DERIVATIVES - IMPLICATION FOR VIRAL FUSION
A MOLECULAR CLASP IN THE HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 TM PROTEIN DETERMINES THE ANTI-HIV ACTIVITY OF GP41 DERIVATIVES - IMPLICATION FOR VIRAL FUSION
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DOI：
10.1128/jvi.69.6.3771-3777.1995
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发表时间：
1995-06-01
影响因子：
5.4
通讯作者：
GREENBERG, ML
中科院分区：
文献类型：
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作者：
CHEN, CH;MATTHEWS, TJ;GREENBERG, ML
我们之前报道过，代表人类免疫缺陷病毒 1 型 (HIV-1) gp41 的亮氨酸拉链结构域 (DP107) 和第二个推定螺旋结构域 (DP178) 的合成肽表现出有效的抗 HIV 活性。在这项研究中，我们使用了 gp41 的可溶性重组形式来提供证据，证明 DP178 肽和 gp41 的 DP178 区域与 gp41 上的远端位点相关。跨膜蛋白，其相互作用结构受亮氨酸拉链 (DP107) 基序影响。我们还观察到亮氨酸拉链结构域中的单个卷曲螺旋破坏突变将重组 gp41 蛋白从无活性的 HIV-1 融合和感染性抑制剂转变为活性抑制剂，这可能与该发现有关。我们推测这种转化是由于从带有亮氨酸拉链的分子扣（DP107）中释放出有效的 DP178 相关序列所致。在 gp41 的两种不同构象的背景下讨论了结果。分子以及这两个结构域可能参与与 HIV-1 介导的融合相关的结构转变。这些结果还被解释为表明各种 gp41 衍生物（肽和重组蛋白）的抗 HIV 活性可能是由于它们能够与病毒 gp41 形成复合物并干扰其融合过程。
We have previously reported that synthetic peptides representing the leucine zipper domain (DP107) and a second putative helical domain (DP178) of human immunodeficiency virus type 1 (HIV-1) gp41 exhibit potent anti-HIV activity, In this study we have used soluble recombinant forms of gp41 to provide evidence that the DP178 peptide and the DP178 region of gp41 associate with a distal site on the gp41 transmembrane protein whose interactive structure is influenced by the leucine zipper (DP107) motif. We also observed that a single coiled-coil-disrupting mutation in the leucine zipper domain transformed the recombinant gp41 protein from an inactive to an active inhibitor of HIV-1 fusion and infectivity, which may be related to that finding. We speculate that this transformation results from liberation of the potent DP178-related sequence from a molecular clasp with a leucine zipper, DP107, determinant. The results are discussed in the context of two distinct conformations for the gp41. molecule and possible involvement of these two domains in structural transitions associated with HIV-1-mediated fusion. The results are also interpreted to suggest that the anti-HIV activity of the various gp41 derivatives (peptides and recombinant proteins) may be due to their ability to form complexes with viral gp41 and interfere with its fusogenic processes.