2. Outer-membrane biogenesis
The outer-membrane (OM) is a permeability barrier that is essential for the viability of Gram- bacteria and protects them against various antibiotics. OM components (lipopolysaccharides, phospholipids, proteins) are synthesized in the cytoplasm or in the inner-membrane. The mechanisms by which unfolded proteins and lipids are then transported through the hydrophilic periplasm and are inserted in the OM are obscure (Figure 2). Our overall goal is to solve the fascinating problem of how such a complex macromolecular structure is assembled in a compartment devoid of energy. The proteins that are involved in OM biogenesis are also attractive targets for the design of new antibiotics and anti-inflammatory drugs.
We have identified new proteins that are involved in maintaining the integrity of the OM and we are currently characterizing them using a combination of biochemistry, proteomics, structural biology and genetics.
Figure 2. The outer-membrane is an asymmetric lipid bilayer with lipopolysaccharides in the outer leaflet and phospholipids in the inner-leaflet. There are proteins present in the outer-membrane, either lipoproteins that are anchored in the membrane but are present in the periplasm, or beta-barrel proteins. We do not know how these components that are assembled in the cytoplasm or in inner-membrane are transported across the periplasm and are assembled in the OM. The YaeT and Imp complexes have been recently identified. They are involved in beta-barrels and lipopolysaccharides insertion, respectively. However, their role and mechanism are poorly understood.
To know more... (pdf chapter of the last de Duve Institute report)
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