IGEM:MIT/2005/Linkers

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Periplasm spanning linkers:
 * Type I secretion in Gram Negative Bacteria


 * Drug Efflux across Two Membranes


 * Summary
 * Efflux pump has 3 components: outer membrane(OM), inner membrane(IM), periplasmic protein
 * Periplasmic components of these pumps are proposed to move the membranes close together
 * Efflux pumps for small molecules and proteins function by different mechanisms
 * Drug Efflux in E. Coli
 * Periplasmic component: AcrA
 * IM: AcrB
 * OM: TolC
 * AcrAB emoves substrates from cell directly into medium
 * TolC proposed to also associate with other several other transport systems
 * AcrB is part of the RND superfamily
 * AcrA is part of the Membrane Fusion Protein
 * OM seem to be interchangeable between different systems
 * Membrane Fusion Protein
 * 2 hydrophobic domains near N/C termini and interact with the IM and OM
 * AcrA also has covalently-linked lipids at N-terminal
 * AcrA = 20nm, highly asymmetric, has alpha-helical region centrally located
 * MFP proposed to work by bringingg the Im and OM together
 * Interaction between the TolC and AcrA Proteins of a Multidrug Efflux System of Escherichia coli
 * Summary
 * There is evidence for the physical interactions between the TolC (outer membrane component) and AcrA (Periplasmic protein) of the drug efflux system in E. Coli
 * TolC and AcrAB must make direct contact to carry out efflux function
 * TolC-AcrA complexes exist in cell independent of AcrB
 * AcrB not needed for AcrA to physically interact with TolC
 * Possible for TolC-AcrA, AcrA-AcrB or TolC-AcrAB complexes to form spontaneously
 * A model of a transmembrane drug-efflux pump from Gram-negative bacteria
 * Note picture below, AcrA may not work the way we want it to


 * AcrA sequence


 * AcrA is a highly asymmetric protein capable of spanning the periplasm.