Structural study of the HIV1 gp41 coat protein

HIV1 gp41外壳蛋白的结构研究

• 批准号: 7967823
• 负责人: Ad Bax
• 金额: $ 28.11万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7967823
• 关键词: Adopted; Capsid Proteins; Characteristics; Chemicals; Complex; Detergents; Exhibits; Flu virus; HIV-1; Hemagglutinin; Homo; Left; Micelles; Molecular; Molecular Conformation; NMR Spectroscopy; Property; Proteins; Sampling; Solutions; Structure; Temperature; Time; Transmembrane Domain; Virus; falls; protein structure

Truncation of the gp41 construct just past its transmembrane domain, leaving residues 1-190, results in a well-structured protein, soluble in dodecylmaltoside while adopting its natural homo-trimeric form. The protein is found to be quite stable, even at temperatures of 50C, and samples are found to be suitable for NMR spectroscopy. Preliminary analysis shows that even thought the ecto-domain resonances are severely broadened, characteristic of slow molecular tumbling, the fusion domains of the trimer yield good NMR spectral characteristics. We find that these fusion domains exhibit chemical shifts that fall very close to those of the isolated domain, previously studied in SDS micelles and found to be uniformly alpha-helical. The fusion domains exhibit effective correlation times that are much shorter than for the remainder of the large trimeric complex, indicating that the intact fusion domain helices are highly mobile within the detergent micelle, while retaining their helical conformation. This excludes the previously hypothesized interaction with the gp41 transmembrane domain.

GP41构建体的截断刚刚超过了其跨膜结构域，使残基1-190产生了结构良好的蛋白质，同时采用其天然同型三晶形式，从而可溶于十二烷基乳糖苷。 即使在50C的温度下，该蛋白也很稳定，并且发现样品适用于NMR光谱法。 初步分析表明，即使认为ecto域的共振也被严重扩展，这是缓慢分子滚动的特征，三聚体的融合结构域产生了良好的NMR光谱特性。我们发现，这些融合结构域表现出非常接近孤立结构域的化学位移，以前在SDS胶束中研究并发现均匀的α-螺旋。融合结构域的有效相关时间比在大型三聚体配合物的其余部分短得多，这表明完整的融合域螺旋在洗涤剂胶束中高度流动，同时保持其螺旋构象。这排除了先前假设的与GP41跨膜结构域的相互作用。