Membrane Disrupting Proteins
Membrane damaging proteins, found widely in biology, are extensively used by microorganisms to cause disease in hosts or attack competing organisms. The proteins must travel to their target in a water soluble state and then insert into the membrane phase.
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K. N. Timmis (ed.), Handbook of Hydrocarbon and Lipid Microbiology, DOI 10.1007/978-3-540-77587-4_30, # Springer-Verlag Berlin Heidelberg, 2010
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Membrane Disrupting Proteins
Abstract: Membrane damaging proteins, found widely in biology, are extensively used by microorganisms to cause disease in hosts or attack competing organisms. The proteins must travel to their target in a water soluble state and then insert into the membrane phase. This chapter deals with the fundamental features of such proteins, highlighting the importance of secondary structure formation during membrane insertion and the role of tryptophan residues in interfacial binding.
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Introduction
Proteins that damage membranes are generally involved in either the promotion of, or inhibition of, pathogenesis in its broadest sense. From bacteria to bees and sea anemones to mammals, membrane damage is used for attack (See > Chapter 68, Vol. 4, Part 7; > Chapter 69, Vol. 3, Part 7; > Chapter 70, Vol. 3, Part 7) and defense (Anderluh and Lakey, 2008). Rearrangement of eukaryotic membranes during normal cell turnover or their destruction during programmed cell death may also use similar mechanisms (See > Chapter 21, Vol. 2, Part 4) but these are less well understood and also not of direct relevance to this review. Whatever the reason for their evolution, the proteins’ main target is to disrupt the impermeability of the cell membrane (Anderluh and Lakey, 2008). The plasma membrane functions by creating a tight barrier between the cytoplasm and the exterior. This is achieved by a 3–5 nm hydrophobic barrier that has to be overcome by water soluble molecules before they enter or exit the cell (See > Chapter 29, Vol. 1, Part 5). Disruption of this barrier has grave consequences for most cells although their sensitivity varies (See > Chapter 43, Vol. 2, Part 7; > Chapter 44, Vol. 2, Part 7; > Chapter 52, Vol. 2, Part 9). Bacteria, with their small internal volumes, often unfriendly external environments and single membrane, which carries out many functions from nutrient uptake to energy conversion, are much more sensitive to small increases in permeability than eukaryotic cells. The latter are relatively large, in protected environments and possessors of a whole range of specialized membrane compartments (Iacovache et al., 2008; Lakey et al., 1994b). It is, however, possible to damage an animal cell which lacks the cell walls found in plants and fungi by colloid osmotic lysis. This occurs when the cell’s water permeability is increased by toxin induced pores. The cell is full of large macromolecules such as proteins, DNA etc which act as impermeable colloids which will not equilibrate across the bilayer. On the other hand water and small solutes enter the cell in response to a lowered water potential and concentration gradients respectively. The cell is unable to mitigate this flux and increases in volume until it lyses. Nevertheless, it has been found that membrane damaging proteins whose targets are eukaryotic often have subtle effects in intracel
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