2014年6月18日， Nature雜誌在線發表了中國科學院生物物理研究所黃億華研究員研究組對細菌脂多糖轉運組裝膜蛋白複合體結構解析重要成果。他們成功地解析了致病菌福氏志賀菌來源的分子量約為110,000道爾頓的LptD-LptE膜蛋白複合體2.4埃的高解析度晶體結構。該晶體結構披露了一種前所未有的由兩個蛋白所形成的「塞子-桶」結構模式，並首次觀察到一個整合膜蛋白（LptD）中含有兩對非連續的、跨結構域的二硫鍵。同時，LptD的跨膜區是迄今所發現的由最多β鏈所組成（由26條β鏈圍成），尺寸最大的β桶狀整合膜蛋白。最為重要的是，在這26條β鏈中, 由於第1條和第2條β鏈各自存在一個脯氨酸, 破壞了其規則二級結構的形成, 從而削弱了和相鄰β鏈之間的相互作用。因此，在組成β桶的第3和第26條β鏈間創造了一個寬度為16埃的脂多糖出口，其大小可以允許脂多糖從桶壁上的出口側向輸入到脂雙層中。該複合體晶體三維結構也很好地解釋了過去近二十年來世界各國生物化學家和細菌遺傳學家對LptD和LptE兩個蛋白所進行的功能研究。
生物谷推薦的英文摘要：
Nature doi:10.1038/nature13484
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)1. The export of LPS requires seven essential lipopolysaccharide transport (Lpt) proteins to move LPS from the inner membrane, through the periplasm to the surface2. Of the seven Lpt proteins, the LptD–LptE complex is responsible for inserting LPS into the external leaflet of the outer membrane3, 4. Here we report the crystal structure of the ~110-kilodalton membrane protein complex LptD–LptE from Shigella flexneri at 2.4?? 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.