LINE BROADENING MECHANISMS IN LANTHANIDE DOPED PHOSPHOLIPID MEMBRANES

镧系元素掺杂磷脂膜的谱线展宽机制

• 批准号: 6465899
• 负责人: STANLEY J OPELLA
• 金额: $ 17.24万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-19 至 2002-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6465899
• 关键词: AIDS; biological products; biomedical resource; immunology; infection; inflammation; lymphatic system; nuclear magnetic resonance spectroscopy; proteins; sexually transmitted diseases; structural biology; virus

The N-terminal 22 residues of the envelope glycoprotein 41,000 (gp41) of HIV have been implicated in the process of viral fusion with the target cell membrane. This gp41 fusion peptide (FP) has a highly conserved hydrophobic sequence, containing a tandem repeat of the tripeptide Phe-Leu-Gly, with extensive homology to the fusion peptides of other paramyxoviruses. FTIR and CD studies and theoretical calculations suggest that the gp41 FP inserts into the phospholipid membrane at an oblique angle, with residues 519 to 533 in an a-helical conformation, and the remaining peptide in a random conformation. Solid-state NMR studies of the selectively 15N labeled gp41 FP were conducted to ascertain the veracity of this model. The petide was incorporated into lipid bilayers and oriented on glass plates. The 15N chemical shift spectrum of gp41 FP labeled in position Ala-524 indicates that the amide bond is oriented with the helix axis paralell to the bilayer normal. The 15N spectra from Ala-253 and Gly-254 reflect a mixture of random and transmembrane conformations, as might be expected for a conformational transition zone. Ala-539 gives an 15N spectrum characteristic of random conformation.

包膜糖蛋白 41,000 的 N 端 22 个残基 HIV 的 (gp41) 与病毒融合过程有关 靶细胞膜。 这种 gp41 融合肽 (FP) 具有高度 保守的疏水序列，包含串联重复 三肽 Phe-Leu-Gly，与融合肽具有广泛的同源性 其他副粘病毒。 FTIR 和 CD 研究与理论 计算表明 gp41 FP 插入磷脂中 膜呈斜角，残基 519 至 533 呈 a 螺旋状 构象，其余肽为随机构象。 选择性 15N 标记的 gp41 FP 的固态 NMR 研究 来验证这个模型的真实性。 肽是 掺入脂质双层并在玻璃板上定向。 这 位置 Ala-524 标记的 gp41 FP 的 15N 化学位移谱 表示酰胺键与螺旋轴平行取向 至双层正常。 Ala-253 和 Gly-254 的 15N 光谱 反映随机和跨膜构象的混合，可能 预计构象过渡区。 Ala-539 给出 随机构象的 15N 谱特征。