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摘要 : 东英吉利大学等处的Haohao Dong等人和中科院生物物理所Shuai Qiao等人发表了分别来自细菌Salmonella typhimurium和Shigella flexneri的脂多糖运输蛋白LptD和LptE之间所形成的复合物的 X-射线晶体结构。相关文章发表于2014年6月18日的《Nature》杂志上。

东英吉利大学等处的Haohao Dong等人和中科院生物物理所Shuai Qiao等人发表了分别来自细菌Salmonella typhimurium和Shigella flexneri的脂多糖运输蛋白LptD和LptE之间所形成的复合物的 X-射线晶体结构。相关文章发表于2014年6月18日的《Nature》杂志上。




Structural basis for outer membrane lipopolysaccharide insertion

Haohao Dong, Quanju Xiang, Yinghong Gu, Zhongshan Wang, Neil G. Paterson, Phillip J. Stansfeld, Chuan He, Yizheng Zhang, Wenjian Wang & Changjiang Dong

Lipopolysaccharide (LPS) is essential for most Gram-negative bacteria and has crucial roles in protection of the bacteria from harsh environments and toxic compounds, including antibiotics. Seven LPS transport proteins (that is, LptA–LptG) form a trans-envelope protein complex responsible for the transport of LPS from the inner membrane to the outer membrane, the mechanism for which is poorly understood. Here we report the first crystal structure of the unique integral membrane LPS translocon LptD–LptE complex. LptD forms a novel 26-stranded β-barrel, which is to our knowledge the largest β-barrel reported so far. LptE adopts a roll-like structure located inside the barrel of LptD to form an unprecedented two-protein ‘barrel and plug’ architecture. The structure, molecular dynamics simulations and functional assays suggest that the hydrophilic O-antigen and the core oligosaccharide of the LPS may pass through the barrel and the lipid A of the LPS may be inserted into the outer leaflet of the outer membrane through a lateral opening between strands β1 and β26 of LptD. These findings not only help us to understand important aspects of bacterial outer membrane biogenesis, but also have significant potential for the development of novel drugs against multi-drug resistant pathogenic bacteria.

Structural basis for lipopolysaccharide insertion in the bacterial outer membrane

Shuai Qiao, Qingshan Luo, Yan Zhao, Xuejun Cai Zhang & Yihua Huang

One of the fundamental properties of biological membranes is the asymmetric distribution of membrane lipids. In Gram-negative bacteria, the outer leaflet of the outer membrane is composed predominantly of lipopolysaccharides (LPS). The export of LPS requires seven essential lipopolysaccharide transport (Lpt) proteins to move LPS from the inner membrane, through the periplasm to the surface. Of the seven Lpt proteins, the LptD–LptE complex is responsible for inserting LPS into the external leaflet of the outer membrane. Here we report the crystal structure of the ~110-kilodalton membrane protein complex LptD–LptE from Shigella flexneri at 2.4 Å resolution. The structure reveals an unprecedented two-protein plug-and-barrel architecture with LptE embedded into a 26-stranded β-barrel formed by LptD. importantly, the secondary structures of the first two β-strands are distorted by two proline residues, weakening their interactions with neighbouring β-strands and creating a potential portal on the barrel wall that could allow lateral diffusion of LPS into the outer membrane. The crystal structure of the LptD–LptE complex opens the door to new antibiotic strategies targeting the bacterial outer membrane.


对应Nature杂志: 2014年7月3日Nature杂志精选

来源: Nature中文 浏览次数:75


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