摘要：SummaryGram-negative bacteria contain an asymmetric outer membrane, in which the outer leaflet is composed of lipopolysaccharide (LPS). LPS, a drug target of polymyxin, plays an essential role in drug resistance, biofilm formation, and pathogenesis. An important inner membrane protein, YciM, may be responsible for the regulation of LPS biosynthesis and transport. Here, we report the crystal structure of YciM fromSalmonella typhimuriumin a complex with a non-specifically bond molecule, an ethylene glycol, which identified a tunnel that could bind lipids. Ourin vitroassays showed that YciM could bind lipid molecules with affinity in the micromolar range, while mutagenic and functional studies confirmed that lipid-binding residues are critical for the function of YciM. Additionally, our data also showed that YciM accurately regulates LPS biosynthesis and transport with YciS, which could help to better understand the regulation mechanism of LPS.Graphical abstractDisplay OmittedHighlights•Identifying a critical lipid binding tunnel of YciS/YciM•The lipid binding tunnel could bind lipid molecules•Mutants of lipid binding tunnel inhibit cell growth severelyBiological sciences; Molecular biology; Microbiology; Bacteriology; Structural biology
