| Structural highlights
Function
LPTD_ECOLI Together with LptE, is involved in the assembly of lipopolysaccharide (LPS) at the surface of the outer membrane. Contributes to n-hexane resistance.[HAMAP-Rule:MF_01411][1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
Lipopolysaccharide (LPS) assembly at the surfaces-exposed leaflet of the bacterial outer membrane (OM) is mediated by the OM LPS translocon. An essential transmembrane beta-barrel protein, LptD, and a cognate lipoprotein, LptE, translocate LPS selectively into the OM external leaflet via a poorly understood mechanism. Here, we characterize two additional translocon subunits, the lipoproteins LptM and LptY (formerly YedD). We use single-particle cryo-EM analysis, functional assays and molecular dynamics simulations to visualize the roles of LptM and LptY at the translocon holo-complex LptDEMY, uncovering their impact on LptD conformational dynamics. Whereas LptY binds and stabilizes the periplasmic LptD beta-taco domain that functions as LPS receptor, LptM intercalates the lateral gate of the beta-barrel domain, promoting its opening and access by LPS. Remarkably, we demonstrate a conformational switch of the LptD beta-taco/beta-barrel interface alternating between contracted and extended states. beta-strand 1 of LptD, which defines the mobile side of the lateral gate, binds LPS and performs a stroke movement toward the external leaflet during the contracted-to-extended state transition. Our findings support a detailed mechanistic framework explaining the selective transport of LPS to the membrane external leaflet.
Structural basis of lipopolysaccharide assembly by the outer membrane translocon holo-complex.,Chen H, Siroy A, Morales V, Gurvic D, Quentin Y, Balor S, Abuta'a YA, Marteau M, Froment C, Caumont-Sarcos A, Marcoux J, Stansfeld PJ, Fronzes R, Ieva R Nat Commun. 2025 Nov 24;16(1):10404. doi: 10.1038/s41467-025-65370-2. PMID:41285762[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Abe S, Okutsu T, Nakajima H, Kakuda N, Ohtsu I, Aono R. n-Hexane sensitivity of Escherichia coli due to low expression of imp/ostA encoding an 87 kDa minor protein associated with the outer membrane. Microbiology. 2003 May;149(Pt 5):1265-73. PMID:12724388
- ↑ Wu T, McCandlish AC, Gronenberg LS, Chng SS, Silhavy TJ, Kahne D. Identification of a protein complex that assembles lipopolysaccharide in the outer membrane of Escherichia coli. Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11754-9. Epub 2006 Jul 21. PMID:16861298 doi:http://dx.doi.org/0604744103
- ↑ 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
- ↑ Chng SS, Ruiz N, Chimalakonda G, Silhavy TJ, Kahne D. Characterization of the two-protein complex in Escherichia coli responsible for lipopolysaccharide assembly at the outer membrane. Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5363-8. doi:, 10.1073/pnas.0912872107. Epub 2010 Mar 4. PMID:20203010 doi:http://dx.doi.org/10.1073/pnas.0912872107
- ↑ Haarmann R, Ibrahim M, Stevanovic M, Bredemeier R, Schleiff E. The properties of the outer membrane localized Lipid A transporter LptD. J Phys Condens Matter. 2010 Nov 17;22(45):454124. doi:, 10.1088/0953-8984/22/45/454124. Epub 2010 Oct 29. PMID:21339611 doi:http://dx.doi.org/10.1088/0953-8984/22/45/454124
- ↑ Sampson BA, Misra R, Benson SA. Identification and characterization of a new gene of Escherichia coli K-12 involved in outer membrane permeability. Genetics. 1989 Jul;122(3):491-501. PMID:2547691
- ↑ Aono R, Negishi T, Nakajima H. Cloning of organic solvent tolerance gene ostA that determines n-hexane tolerance level in Escherichia coli. Appl Environ Microbiol. 1994 Dec;60(12):4624-6. PMID:7811102
- ↑ Chen H, Siroy A, Morales V, Gurvič D, Quentin Y, Balor S, Abuta'a YA, Marteau M, Froment C, Caumont-Sarcos A, Marcoux J, Stansfeld PJ, Fronzes R, Ieva R. Structural basis of lipopolysaccharide assembly by the outer membrane translocon holo-complex. Nat Commun. 2025 Nov 24;16(1):10404. PMID:41285762 doi:10.1038/s41467-025-65370-2
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