表没食子儿茶素-3-没食子酸酯能快速重塑PAP85-120、SEM1(45-107)和SEM2(49-107)精浆淀粉样纤维。
Epigallocatechin-3-gallate rapidly remodels PAP85-120, SEM1(45-107), and SEM2(49-107) seminal amyloid fibrils.
作者信息
Castellano Laura M, Hammond Rebecca M, Holmes Veronica M, Weissman Drew, Shorter James
机构信息
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA Pharmacology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA Department of Biology, Swarthmore College, Swarthmore, PA 19081, USA.
出版信息
Biol Open. 2015 Aug 28;4(9):1206-12. doi: 10.1242/bio.010215.
Semen harbors amyloid fibrils formed by proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120) and semenogelins (SEM1 and SEM2) that potently enhance HIV infectivity. Amyloid but not soluble forms of these peptides enhance HIV infection. Thus, agents that remodel these amyloid fibrils could prevent HIV transmission. Here, we confirm that the green tea polyphenol, epigallocatechin-3-gallate (EGCG), slowly remodels fibrils formed by PAP248-286 termed SEVI (semen derived enhancer of viral infection) and also exerts a direct anti-viral effect. We elucidate for the first time that EGCG remodels PAP85-120, SEM1(45-107), and SEM2(49-107) fibrils more rapidly than SEVI fibrils. We establish EGCG as the first small molecule that can remodel all four classes of seminal amyloid. The combined anti-amyloid and anti-viral properties of EGCG could have utility in preventing HIV transmission.
精液中含有由前列腺酸性磷酸酶（PAP248 - 286和PAP85 - 120）和精液凝胶蛋白（SEM1和SEM2）的蛋白水解片段形成的淀粉样纤维，这些纤维能有效增强HIV的感染性。这些肽的淀粉样形式而非可溶性形式会增强HIV感染。因此，重塑这些淀粉样纤维的药物可能预防HIV传播。在此，我们证实绿茶多酚表没食子儿茶素 - 3 - 没食子酸酯（EGCG）能缓慢重塑由PAP248 - 286形成的名为SEVI（精液衍生病毒感染增强剂）的纤维，并且还具有直接的抗病毒作用。我们首次阐明，EGCG重塑PAP85 - 120、SEM1(45 - 107)和SEM2(49 - 107)纤维的速度比SEVI纤维更快。我们确定EGCG是首个能够重塑所有四类精液淀粉样蛋白的小分子。EGCG的抗淀粉样蛋白和抗病毒特性相结合，可能在预防HIV传播方面具有效用。
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