Structural and functional properties of peptides based on the N-terminus of HIV-1 gp41 and the C-terminus of the amyloid-beta protein
Structural and functional properties of peptides based on the N-terminus of HIV-1 gp41 and the C-terminus of the amyloid-beta protein
复制标题
DOI：
10.1016/j.bbamem.2008.05.002
复制
发表时间：
2008-10-01
影响因子：
3.4
通讯作者：
Mobley, Patrick W.
中科院分区：
文献类型：
--
作者：
Gordon, Larry M.;Nisthal, Alex;Mobley, Patrick W.
鉴于丙氨酸和甘氨酸水平高、斑块形成、α-螺旋到β-折叠的相互转化和融合性，FP（即 HIV-1 gp41 的 N 端融合肽；23 个残基）和淀粉样蛋白被认为属于同一蛋白质超家族。在这里，我们通过将 FP 的结构和功能特性与 A beta(26-42) 的结构和功能特性进行对比，进一步测试 FP 是否可能表现出“淀粉样蛋白样”特征，A beta (26-42) 是一种来自导致阿尔茨海默病的淀粉样蛋白 C 末端的 17 个残基肽。 FTIR 光谱、电子显微镜、光散射和预测的淀粉样蛋白结构聚集 (PASTA) 表明，水性 FP 和 A beta (26-42) 形成类似的网状 β-片层原纤维，尽管 FP 原纤维相互作用较弱。 FP 和 A beta (26-42) 均裂解并聚集人红细胞，溶血发生与脂质体中每种肽的 α 螺旋转化为 V,β 折叠相关。刚果红 (CR) 是原位淀粉样斑块的标记物，同样可以抑制 FP 或 A beta(26-42) 诱导的溶血，表面等离子体共振表明这可能是由于直接 CR 肽结合所致。这些发现表明，FP 的膜结合 β 片层可能通过淀粉样蛋白型机制促进 HIV 体内的细胞病变，并支持将 HIV-1 FP 分类为“淀粉样蛋白同系物”（或“淀粉样蛋白”）。 (C) 2008 Elsevier B.V. 保留所有权利。
Given their high alanine and glycine levels, plaque formation, alpha-helix to beta-sheet interconversion and fusogenicity, FP (i.e., the N-terminal fusion peptide of HIV-1 gp41; 23 residues) and amyloids were proposed as belonging to the same protein superfamily. Here, we further test whether FP may exhibit 'amyloid-like' characteristics, by contrasting its structural and functional properties with those of A beta(26-42), a 17-residue peptide from the C-terminus of the amyloid-beta protein responsible for Alzheimer's. FTIR spectroscopy, electron microscopy, light scattering and predicted amyloid structure aggregation (PASTA) indicated that aqueous FP and A beta (26-42) formed similar networked beta-sheet fibrils, although the FP fibril interactions were weaker. FP and A beta (26-42) both lysed and aggregated human erythrocytes, with the hemolysis-onsets correlated with the conversion of a-helix to V,beta-sheet for each peptide in liposomes. Congo red (CR), a marker of amyloid plaques in situ, similarly inhibited either FP- or A beta(26-42)-induced hemolysis, and surface plasmon resonance indicated that this may be due to direct CR-peptide binding. These findings suggest that membrane-bound beta-sheets of FP may contribute to the cytopathicity of HIV in vivo through an amyloid-type mechanism, and support the classification of HIV-1 FP as an 'amyloid homolog' (or 'amylog'). (C) 2008 Elsevier B.V. All rights reserved.