CsgG形成的跨膜九聚体通道结构

    2014年12月3日讯 /药家网YAOJIA/ --2014年12月1日，PNAS杂志最近发表了来自中国科学院生物物理研究所黄亿华等人题为《Structure of the nonameric bacterial amyloid secretion channel》的研究成果，详细介绍了它们对对负责细菌表面淀粉样纤维（β-amyloids）分泌通道的结构解析成果。
    随着医疗技术的提高，人们已经征服了许多重大疾病。不幸的是截止到目前为止，人们对于以阿尔兹海默症为代表的神经退行性疾病仍然束手无策。淀粉样纤维蛋白一直被认为与这些神经退行性疾病有着密切关系。因此在这一领域的研究也成为近年来生物研究的热点。在细菌表面，存在一类功能性的淀粉样纤维（Curli）， 为细菌形成菌膜（biofilm）所必需。黄亿华研究组成功解析了负责curli分泌的通道蛋白CsgG九聚体2.9埃的晶体结构。研究显示，CsgG通过9聚化，由每个单体贡献4条跨膜β链，形成了一个跨越细菌外膜由36条β链所组成的分泌通道。这是目前已知的在细菌外膜上最大的、由最多β链所围成的β桶状整合膜蛋白。该通道的选择性由向内突出的氨基酸形成的垛叠环限制，大小只有12 埃，表明组成curli的亚基是以一种未折叠的方式穿过CsgG通道。在结构的基础上，通过细菌遗传学实验和生物化学分析，阐释了功能性淀粉样纤维生物生成的机理，并可为设计抑制菌膜形成的新型抗生素提供重要信息。（药家网yaojia.org）

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PNAS doi: 10.1073/pnas.1411942111
Structure of the nonameric bacterial amyloid secretion channel
Baohua Cao, Yan Zhao, Yongjun Kou, Dongchun Ni，Xuejun Cai Zhang, and Yihua Huang
Various strains of bacteria are able to produce a unique class of functional amyloids termed curli, which are critical for biofilm formation, host cell adhesion, and colonization of inert surfaces. Curli are secreted via the type VIII bacterial secretion system, and they share biochemical and structural characteristics with amyloid fibers that have been implicated in deleterious disease in humans. Here, we report the crystal structure of Escherichia coli CsgG, which is an essential lipoprotein component of the type VIII secretion system and which forms a secretion channel in the bacterial outer membrane for transporting curli subunits. CsgG forms a crown-shaped, symmetric nonameric channel that spans the outer membrane via a 36-strand β-barrel, with each subunit contributing four β-strands. This nonameric complex contains a central channel with a pore located at the middle. The eyelet of the pore is ～12 ? in diameter and is lined with three stacked nine-residue rings consisting of Tyr-66, Asn-70, or Phe-71. Our structure-based functional studies suggest that Tyr-66 and Phe-71 residues function as gatekeepers for the selective secretion of curli subunits. Our study describes in detail, to our knowledge, the first core structure of the type VIII bacterial secretion machinery. Importantly, our structural analysis suggests that the curli subunits are secreted via CsgG across the bacterial outer membrane in an unfolded form.