Conformational analysis of a new peptide derived from feline immunodeficiency virus gp36 in SDS micelles: An NMR-MD based investigation

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Angelo Santoro, Michela Buonocore, Mohammad Firoznezhad, Manuela Grimaldi, Anna Maria D'Ursi
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引用次数: 0

Abstract

Feline immunodeficiency virus (FIV) shares structural similarities with human immunodeficiency virus (HIV): the surface glycoprotein gp36 corresponds to the HIV gp41, which drives virus-host cell interactions and is targeted by the peptide entry inhibitor enfuvirtide. Following a similar drug design strategy for the development of an anti-FIV therapy, the present study investigates 627-646gp36 NHR, a peptide sequence derived from a region of gp36 that was previously found to interfere with the antiviral activity of the peptide C8, which instead derives from the gp36 MPER. CD, NMR, and MD simulations were employed to probe the conformational characteristics of 627-646gp36 NHR in the membrane-mimicking environment of SDS micelles. Our data show that 627-646gp36 NHR is characterized by three dynamic helix structures. MD simulations involving 627-646gp36 NHR, C8, and a larger protein, including the CHR and MPER regions, suggest that the interaction of C8 with the MPER region, the origin of the antiviral activity of C8, is disfavored in the presence of 627-646gp36 NHR in the simulation. This evidence can be useful for interpreting the molecular mechanism that leads to interference with the activity of C8, providing information on the folding/unfolding mechanism of the viral glycoprotein to design new strategies to inhibit viral entry.

猫免疫缺陷病毒 gp36 的新肽在 SDS 胶束中的构象分析:基于 NMR-MD 的研究。
猫免疫缺陷病毒(FIV)与人类免疫缺陷病毒(HIV)在结构上有相似之处:其表面糖蛋白gp36与HIV的gp41相对应,后者驱动着病毒与宿主细胞的相互作用,并且是多肽进入抑制剂恩夫韦肽的靶标。为了开发抗 FIV 疗法,本研究采用了类似的药物设计策略,研究了 627-646gp36 NHR,该肽序列来自 gp36 的一个区域,以前曾发现该区域干扰了肽 C8 的抗病毒活性,而 C8 则来自 gp36 MPER。我们利用 CD、NMR 和 MD 模拟来探究 627-646gp36 NHR 在 SDS 胶束的膜模拟环境中的构象特征。我们的数据显示,627-646gp36 NHR 具有三种动态螺旋结构。涉及 627-646gp36 NHR、C8 和一个更大的蛋白质(包括 CHR 和 MPER 区域)的 MD 模拟表明,在模拟中存在 627-646gp36 NHR 的情况下,不利于 C8 与 MPER 区域(C8 抗病毒活性的起源)的相互作用。这一证据有助于解释导致干扰 C8 活性的分子机制,为设计抑制病毒进入的新策略提供病毒糖蛋白折叠/解折机制方面的信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Peptide Science
Journal of Peptide Science 生物-分析化学
CiteScore
3.40
自引率
4.80%
发文量
83
审稿时长
1.7 months
期刊介绍: The official Journal of the European Peptide Society EPS The Journal of Peptide Science is a cooperative venture of John Wiley & Sons, Ltd and the European Peptide Society, undertaken for the advancement of international peptide science by the publication of original research results and reviews. The Journal of Peptide Science publishes three types of articles: Research Articles, Rapid Communications and Reviews. The scope of the Journal embraces the whole range of peptide chemistry and biology: the isolation, characterisation, synthesis properties (chemical, physical, conformational, pharmacological, endocrine and immunological) and applications of natural peptides; studies of their analogues, including peptidomimetics; peptide antibiotics and other peptide-derived complex natural products; peptide and peptide-related drug design and development; peptide materials and nanomaterials science; combinatorial peptide research; the chemical synthesis of proteins; and methodological advances in all these areas. The spectrum of interests is well illustrated by the published proceedings of the regular international Symposia of the European, American, Japanese, Australian, Chinese and Indian Peptide Societies.
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