5nuq
Structural basis for maintenance of bacterial outer membrane lipid asymmetry
Structural highlights
FunctionOMPF_ECOLI Forms pores that allow passive diffusion of small molecules across the outer membrane. It is also a receptor for the bacteriophage T2.[1] Publication Abstract from PubMedThe Gram-negative bacterial outer membrane (OM) is a unique bilayer that forms an efficient permeation barrier to protect the cell from noxious compounds 1,2 . The defining characteristic of the OM is lipid asymmetry, with phospholipids comprising the inner leaflet and lipopolysaccharides comprising the outer leaflet 1-3 . 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 4 . 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 alpha-helical OM protein that functions as a phospholipid translocation channel, forming a ~20-A-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 5,6 , 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.The crystal structure of MlaA, coupled with simulations of its interaction with phospholipids, elucidates how this outer membrane lipoprotein acts as a phospholipid translocation channel to maintain the asymmetric composition of the outer membrane. Structural basis for maintenance of bacterial outer membrane lipid asymmetry.,Abellon-Ruiz J, Kaptan SS, Basle A, Claudi B, Bumann D, Kleinekathofer U, van den Berg B Nat Microbiol. 2017 Oct 16. doi: 10.1038/s41564-017-0046-x. PMID:29038444[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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