6gd5 | pdb_00006gd5
The solution structure of the LptA-Thanatin complex
Structural highlights
Function[LPTA_ECOLI] Involved in the assembly of lipopolysaccharide (LPS). Required for the translocation of LPS from the inner membrane to the outer membrane. May form a bridge between the inner membrane and the outer membrane, via interactions with LptC and LptD, thereby facilitating LPS transfer across the periplasm.[HAMAP-Rule:MF_01914][1] [2] [3] [4] [5] [THAN_PODMA] Insect defense peptide with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and fungi. No activity against S.aureus. Stops respiration in bacteria but does not permeabilize their inner membranes. Publication Abstract from PubMedWith the increasing resistance of many Gram-negative bacteria to existing classes of antibiotics, identifying new paradigms in antimicrobial discovery is an important research priority. Of special interest are the proteins required for the biogenesis of the asymmetric Gram-negative bacterial outer membrane (OM). Seven Lpt proteins (LptA to LptG) associate in most Gram-negative bacteria to form a macromolecular complex spanning the entire envelope, which transports lipopolysaccharide (LPS) molecules from their site of assembly at the inner membrane to the cell surface, powered by adenosine 5'-triphosphate hydrolysis in the cytoplasm. The periplasmic protein LptA comprises the protein bridge across the periplasm, which connects LptB2FGC at the inner membrane to LptD/E anchored in the OM. We show here that the naturally occurring, insect-derived antimicrobial peptide thanatin targets LptA and LptD in the network of periplasmic protein-protein interactions required to assemble the Lpt complex, leading to the inhibition of LPS transport and OM biogenesis in Escherichia coli. Thanatin targets the intermembrane protein complex required for lipopolysaccharide transport in Escherichia coli.,Vetterli SU, Zerbe K, Muller M, Urfer M, Mondal M, Wang SY, Moehle K, Zerbe O, Vitale A, Pessi G, Eberl L, Wollscheid B, Robinson JA Sci Adv. 2018 Nov 14;4(11):eaau2634. doi: 10.1126/sciadv.aau2634. eCollection, 2018 Nov. PMID:30443594[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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