Haemolytic actinoporins interact with carbohydrates using their lipid-binding module.
Haemolytic actinoporins interact with carbohydrates using their lipid-binding module.
复制标题
溶血放线菌蛋白利用其脂质结合模块与碳水化合物相互作用。
DOI：
10.1098/rstb.2016.0216
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Morante K and Tsumoto K.
中科院分区：
文献类型：
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作者：
Tanaka K;Caaveiro JMM;Morante K and Tsumoto K.
成孔毒素（PFT）是一种具有变质特性的蛋白质，使其能够在水溶液和细胞膜中稳定折叠。 PFT 在靶细胞质膜上产生有利于病变的溶解孔，在生物体的防御和进攻分子系统中发挥关键作用。放线孔蛋白是海葵产生的一类强效溶血毒素，在脂质-蛋白质相互作用的背景下，并与纳米孔技术相关，作为 α-螺旋 PFT 的范例，得到了广泛的研究。我们最近报道，山毛榉毒素 C (FraC) 是一种放线孔蛋白，它通过大的粘附基序与生物膜结合，允许在孔形成之前同时附着多达四个脂质分子。由于放线菌素也与碳水化合物相互作用，我们试图了解 FraC 识别聚糖的分子和能量基础。通过采用结构和生物物理方法，我们表明 FraC 使用其脂质结合模块以低亲和力接合聚糖。与其他需要单独的域进行聚糖和脂质识别的 PFT 不同，小型单域放线孔蛋白通过使用单个结合模块实现双重识别来节省资源。这种机制可以增强放线菌蛋白在海洋环境中向目标组织表面的募集。本文是“膜孔：从结构和组装到医学和技术”主题的一部分。
Pore-forming toxins (PFTs) are proteins endowed with metamorphic properties that enable them to stably fold in water solutions as well as in cellular membranes. PFTs produce lytic pores on the plasma membranes of target cells conducive to lesions, playing key roles in the defensive and offensive molecular systems of living organisms. Actinoporins are a family of potent haemolytic toxins produced by sea anemones vigorously studied as a paradigm of α-helical PFTs, in the context of lipid–protein interactions, and in connection with nanopore technologies. We have recently reported that fragaceatoxin C (FraC), an actinoporin, engages biological membranes with a large adhesive motif allowing the simultaneous attachment of up to four lipid molecules prior to pore formation. Since actinoporins also interact with carbohydrates, we sought to understand the molecular and energetic basis of glycan recognition by FraC. By employing structural and biophysical methodologies, we show that FraC engages glycans with low affinity using its lipid-binding module. Contrary to other PFTs requiring separate domains for glycan and lipid recognition, the small single-domain actinoporins economize resources by achieving dual recognition with a single binding module. This mechanism could enhance the recruitment of actinoporins to the surface of target tissues in their marine environment.This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.