IGEM:MIT/2005/Linkers

We're awesome.

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.