Cryo-EM structures of lipopolysaccharide transporter LptB2FGC in lipopolysaccharide or AMP-PNP-bound states reveal its transport mechanism.
Xiaodi TangShenghai ChangQinghua LuoZhengyu ZhangWen QiaoCaihuang XuChangbin ZhangYang NiuWenxian YangTing WangZhibo ZhangXiaofeng ZhuXiawei WeiChangjiang DongXing ZhangHaohao DongPublished in: Nature communications (2019)
Lipopolysaccharides (LPS) of Gram-negative bacteria are critical for the defence against cytotoxic substances and must be transported from the inner membrane (IM) to the outer membrane (OM) through a bridge formed by seven membrane proteins (LptBFGCADE). The IM component LptB2FG powers the process through a yet unclarified mechanism. Here we report three high-resolution cryo-EM structures of LptB2FG alone and complexed with LptC (LptB2FGC), trapped in either the LPS- or AMP-PNP-bound state. The structures reveal conformational changes between these states and substrate binding with or without LptC. We identify two functional transmembrane arginine-containing loops interacting with the bound AMP-PNP and elucidate allosteric communications between the domains. AMP-PNP binding induces an inward rotation and shift of the transmembrane helices of LptFG and LptC to tighten the cavity, with the closure of two lateral gates, to eventually expel LPS into the bridge. Functional assays reveal the functionality of the LptF and LptG periplasmic domains. Our findings shed light on the LPS transport mechanism.
Keyphrases
- protein kinase
- inflammatory response
- high resolution
- anti inflammatory
- lps induced
- toll like receptor
- genome wide
- single cell
- nitric oxide
- high throughput
- dna binding
- molecular dynamics
- minimally invasive
- drinking water
- gene expression
- dna methylation
- molecular dynamics simulations
- binding protein
- immune response
- transcription factor