5NUP

Structural basis for maintenance of bacterial outer membrane lipid asymmetry

Summary for 5NUP

• Entry DOI: 10.2210/pdb5nup/pdb
• Descriptor: OmpK36, ABC transporter permease, (HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE, ... (4 entities in total)
• Functional Keywords: outer membrane, lipid asymmetry, lipoprotein, phospholipid translocation, membrane protein
• Biological source: Klebsiella pneumoniae; More
• Cellular location: Cell outer membrane ; Multi-pass membrane protein : D6QLY0
• Total number of polymer chains: 6
• Total formula weight: 200540.55

Authors

Abellon-Ruiz, J.,Kaptan, S.S.,Basle, A.,Claudi, B.,Bumann, D.,Kleinekathofer, U.,van den Berg, B. (deposition date: 2017-05-01, release date: 2017-10-25, Last modification date: 2024-01-17)

Primary citation

Abellon-Ruiz, J.,Kaptan, S.S.,Basle, A.,Claudi, B.,Bumann, D.,Kleinekathofer, U.,van den Berg, B.
Structural basis for maintenance of bacterial outer membrane lipid asymmetry.
Nat Microbiol, 2:1616-1623, 2017

PubMed Abstract: The Gram-negative bacterial outer membrane (OM) is a unique bilayer that forms an efficient permeation barrier to protect the cell from noxious compounds . The defining characteristic of the OM is lipid asymmetry, with phospholipids comprising the inner leaflet and lipopolysaccharides comprising the outer leaflet . This asymmetry is maintained by the Mla pathway, a six-component system that is widespread in Gram-negative bacteria and is thought to mediate retrograde transport of misplaced phospholipids from the outer leaflet of the OM to the cytoplasmic membrane . The OM lipoprotein MlaA performs the first step in this process via an unknown mechanism that does not require external energy input. Here we show, using X-ray crystallography, molecular dynamics simulations and in vitro and in vivo functional assays, that MlaA is a monomeric α-helical OM protein that functions as a phospholipid translocation channel, forming a ~20-Å-thick doughnut embedded in the inner leaflet of the OM with a central, amphipathic pore. This architecture prevents access of inner leaflet phospholipids to the pore, but allows outer leaflet phospholipids to bind to a pronounced ridge surrounding the channel, followed by diffusion towards the periplasmic space. Enterobacterial MlaA proteins form stable complexes with OmpF/C , but the porins do not appear to play an active role in phospholipid transport. MlaA represents a lipid transport protein that selectively removes outer leaflet phospholipids to help maintain the essential barrier function of the bacterial OM.

PubMed: 29038444
DOI: 10.1038/s41564-017-0046-x

Experimental method

X-RAY DIFFRACTION (2.9 Å)