Structural characterization of semen coagulum-derived SEM1(86-107) amyloid fibrils that enhance HIV-1 infection.

Structural characterization of semen coagulum-derived SEM1(86-107) amyloid fibrils that enhance HIV-1 infection.
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DOI:
10.1021/bi500427r
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发表时间:
2014-05-27
期刊:
影响因子:
2.9
通讯作者:
Makhatadze GI
Makhatadze GI
中科院分区:
生物学3区
文献类型:
--
作者:
French KC;Roan NR;Makhatadze GI

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SEM1(86–107) 是一种 22 残基肽,对应于精蛋白 I 蛋白中的残基 86–107。 SEM1(86–107) 是新鲜液化精液的丰富成分,并形成能够增强 HIV 感染的淀粉样原纤维。为了探讨影响原纤维形成的因素并更好地了解精液和阴道液之间的 pH 值差异如何影响原纤维稳定性,本研究确定了 pH 对 SEM1(86–107) 原纤维形成和解离的影响。还使用氢-氘交换质谱 (HDXMS) 和羟基自由基介导的蛋白质修饰来探测 SEM1(86–107) 原纤维结构(即构成原纤维核心的残基)。 SEM1(86-107) 原纤维中羟基自由基介导修饰的平均暴露百分比无需串联质谱采集或修饰肽的完全分离即可确定。结果发现,通过 HDXMS 和羟基自由基介导的修饰计算出的残留物暴露量相似。这些技术证明 SEM1(86–107) 的三个区域包含淀粉样蛋白原纤维核心,并且暴露出带正电的残基,这表明 SEM1(86–107) 与 HIV 或细胞表面之间的静电相互作用可能是通过 SEM1(86–107) 原纤维介导 HIV 感染增强的原因。
SEM1(86–107) is a 22-residue peptide corresponding to residues 86–107 in the semenogelin I protein. SEM1(86–107) is an abundant component of freshly liquefied semen and forms amyloid fibrils capable of enhancing HIV infection. To probe the factors affecting fibril formation and gain a better understanding of how differences in pH between semen and vaginal fluid affect fibril stability, this study determined the effect of pH on SEM1(86–107) fibril formation and dissociation. The SEM1(86–107) fibril structure (i.e., residues that comprise the fibrillar core) was also probed using hydrogen–deuterium exchange mass spectrometry (HDXMS) and hydroxyl radical-mediated protein modification. The average percent exposure to hydroxyl radical-mediated modification in the SEM1(86–107) fibrils was determined without requiring tandem mass spectrometry spectral acquisition or complete separation of modified peptides. It was found that the residue exposures calculated from HDXMS and hydroxyl radical-mediated modification were similar. These techniques demonstrated that three regions of SEM1(86–107) comprise the amyloid fibril core and that positively charged residues are exposed, suggesting that electrostatic interactions between SEM1(86–107) and HIV or the cell surface may be responsible for mediating HIV infection enhancement by the SEM1(86–107) fibrils.
DOI: 10.1021/bi301406d
发表时间: 2012-12-21
期刊: Biochemistry
影响因子: 2.9
作者:
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通讯作者: Makhatadze GI
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