The amyloidogenic SEVI precursor, PAP248-286, is highly unfolded in solution despite an underlying helical tendency.
The amyloidogenic SEVI precursor, PAP248-286, is highly unfolded in solution despite an underlying helical tendency.
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DOI：
10.1016/j.bbamem.2011.01.010
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发表时间：
2011-04
影响因子：
3.4
通讯作者：
Ramamoorthy, Ayyalusamy
中科院分区：
文献类型：
--
作者：
Brender, Jeffrey R.;Nanga, Ravi Prakash Reddy;Popovych, Nataliya;Soong, Ronald;Macdonald, Peter M.;Ramamoorthy, Ayyalusamy
人类精液中的淀粉样蛋白纤维被称为SEVI（精液衍生的病毒感染增强剂），可显著增加HIV和其他包膜病毒的感染性，这似乎与促进桥接相互作用和中和宿主与病毒细胞膜之间的静电排斥有关。SEVI前体PAP 248 -286在与去污剂胶束结合时大部分是无序的，与大多数淀粉样蛋白的高度α-螺旋结构相反。为确定该差异的来源，将PAP 248 -286的结构溶于水溶液中，并加入30%和50%三氟乙醇。在溶液中，脉冲场梯度（PFG）-NMR和1H-1H NOESY实验表明，PAP 248 -286是展开到一个不寻常的程度的淀粉样蛋白生成肽，但采用显着的螺旋结构在TFE溶液中。TFE和SDS中PAP 248 -286结构之间的明显差异表明静电相互作用在肽的折叠中起很大作用，与PAP 248 -286渗透到胶束疏水核心的轻微程度一致。这是PAP 248 -286和其他淀粉样肽之间的另一个显著差异，这些淀粉样肽通常至少渗透到双层的头基区域，并可以解释SEVI的一些不寻常的特性。
Amyloid fibers in human semen known as SEVI (Semen-derived Enhancer of Viral Infection) dramatically increase the infectivity of HIV and other enveloped viruses, which appears to be linked to the promotion of bridging interactions and the neutralization of electrostatic repulsion between the host and the viral cell membranes. The SEVI precursor PAP248-286 is mostly disordered when bound to detergent micelles, in contrast to the highly α-helical structures found for most amyloid proteins. To determine the origin of this difference, the structures of PAP248-286 were solved in aqueous solution and with 30% and 50% trifluoroethanol. In solution, pulsed field gradient (PFG)-NMR and 1H-1H NOESY experiments indicate that PAP248-286 is unfolded to an unusual degree for an amyloidogenic peptide but adopts significantly helical structures in TFE solutions. The clear differences between the structures of PAP248-286 in TFE and SDS indicate electrostatic interactions play a large role in the folding of the peptide, consistent with the slight degree of penetration of PAP248-286 into the hydrophobic core of the micelle. This is another noticeable difference between PAP248-286 and other amyloid peptides, which generally show penetration into at least the headgroup region of the bilayer, and may explain some of the unusual properties of SEVI.
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