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Molecular Characterization and Gene Expression Profiling ... - CUSAT

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Chapter 1<br />

lipid head groups (Matsuzaki, et al., 1996). This type of transmembrane pore<br />

is induced by magainins, protegrins <strong>and</strong> melittin (Matsuzaki et al., 1996;<br />

Yang et al., 2001; Hallock et al., 2003). In forming a toroidal pore, the polar<br />

faces of the peptides associate with the polar head groups of the lipids<br />

(Yamaguchi et al., 2002). The lipids in these openings then tilt from the<br />

lamellar normal <strong>and</strong> connect the two leaflets of the membrane, forming a<br />

continuous bend from the top to the bottom in the fashion of a toroidal hole;<br />

the pore is lined by both the peptides <strong>and</strong> the lipid head groups, which are<br />

likely to screen <strong>and</strong> mask cationic peptide charges (Yang et al., 2001). The<br />

toroidal model differs from the barrel-stave model as the peptides are always<br />

associated with the lipid head groups even when they are perpendicularly<br />

inserted in the lipid bilayer (Yang et al., 2001). Magainin-induced toroidal<br />

pores are larger <strong>and</strong> have a more variable pore size than alamethicin-<br />

induced pores (Yang et al., 2001). They have an inner diameter of 3.0–5.0 nm<br />

<strong>and</strong> an outer diameter of ~7.0–8.4 nm, <strong>and</strong> each pore is thought to contain<br />

only 4–7 magainin monomers <strong>and</strong> ~90 lipid molecules (Matsuzaki et al.,<br />

1997, 1998; Yang et al., 2001). The mechanisms of defensins are not as well<br />

defined (Zasloff, 2002; Lehrer, 2004) but they also permeabilize membrane<br />

bilayers containing negatively charged phospholipids (Fujii et al., 1993;<br />

Zasloff, 2002; Lehrer, 2004). Although descriptions of membrane damage<br />

seem to vary, they are likely to be related. It has been suggested that ion<br />

channels, transmembrane pores <strong>and</strong> extensive membrane rupture do not<br />

represent three completely different modes of action, but instead are a<br />

continuous gradation between them (Dathe <strong>and</strong> Wieprecht, 1999).<br />

1.7.10.4 Models of intracellular killing<br />

Although the formation of ion channels, transmembrane pores <strong>and</strong><br />

extensive membrane rupture eventually leads to the lysis of microbial cells,<br />

there is increasing speculation that these effects are not the only mechanisms<br />

of microbial killing. There is increasing evidence to indicate that AMPs have<br />

<strong>Molecular</strong> <strong>Characterization</strong> <strong>and</strong> <strong>Gene</strong> <strong>Expression</strong> <strong>Profiling</strong> of Antimicrobial Peptides in Penaeid Shrimps<br />

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