| 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 PubMed
With 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
- ↑ Sperandeo P, Pozzi C, Deho G, Polissi A. Non-essential KDO biosynthesis and new essential cell envelope biogenesis genes in the Escherichia coli yrbG-yhbG locus. Res Microbiol. 2006 Jul-Aug;157(6):547-58. Epub 2006 Feb 9. PMID:16765569 doi:10.1016/j.resmic.2005.11.014
- ↑ Sperandeo P, Cescutti R, Villa R, Di Benedetto C, Candia D, Deho G, Polissi A. Characterization of lptA and lptB, two essential genes implicated in lipopolysaccharide transport to the outer membrane of Escherichia coli. J Bacteriol. 2007 Jan;189(1):244-53. Epub 2006 Oct 20. PMID:17056748 doi:http://dx.doi.org/10.1128/JB.01126-06
- ↑ Sperandeo P, Lau FK, Carpentieri A, De Castro C, Molinaro A, Deho G, Silhavy TJ, Polissi A. Functional analysis of the protein machinery required for transport of lipopolysaccharide to the outer membrane of Escherichia coli. J Bacteriol. 2008 Jul;190(13):4460-9. Epub 2008 Apr 18. PMID:18424520 doi:JB.00270-08
- ↑ Tran AX, Trent MS, Whitfield C. The LptA protein of Escherichia coli is a periplasmic lipid A-binding protein involved in the lipopolysaccharide export pathway. J Biol Chem. 2008 Jul 18;283(29):20342-9. doi: 10.1074/jbc.M802503200. Epub 2008 , May 14. PMID:18480051 doi:http://dx.doi.org/10.1074/jbc.M802503200
- ↑ Sperandeo P, Villa R, Martorana AM, Samalikova M, Grandori R, Deho G, Polissi A. New insights into the Lpt machinery for lipopolysaccharide transport to the cell surface: LptA-LptC interaction and LptA stability as sensors of a properly assembled transenvelope complex. J Bacteriol. 2011 Mar;193(5):1042-53. doi: 10.1128/JB.01037-10. Epub 2010 Dec 17. PMID:21169485 doi:http://dx.doi.org/10.1128/JB.01037-10
- ↑ 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. Thanatin targets the intermembrane protein complex required for lipopolysaccharide transport in Escherichia coli. Sci Adv. 2018 Nov 14;4(11):eaau2634. doi: 10.1126/sciadv.aau2634. eCollection, 2018 Nov. PMID:30443594 doi:http://dx.doi.org/10.1126/sciadv.aau2634
|
