Biomedical Engineering Reference
In-Depth Information
c
Fig. 7.3 Views of the surface of SHaPrP(90-231) colored according to the electrostatic potential
[ 22 ], with blue for positive charges and red for negative charges, for the protein represented in ( a )
and ( c )atpH7and( b )and( d )atpH5.Views a and b are similar orientations of the molecule, and
c and d are views following a 180 rotation about a vertical axis of ( a )and( b ), respectively. This
figure has been adapted from the Ref. [ 38 ] with permission from the publisher
PrP to negatively charged lipid membranes involves both electrostatic and hydropho-
bic lipid-protein interactions. This results in partial insertion of PrP into the lipid
bilayer. This membrane-inserted conformation of PrP is richer in
-sheet structures,
and has a disruptive effect on the integrity of the lipid bilayer, leading to total release
of vesicle contents. In contrast, this report also suggests that the binding of PrP to
raft-like membranes is driven by hydrophobic lipid-protein interactions, and induces
the formation of
β
α
-helical structures. This conformation of PrP with a high content
of
-helix is formed only at pH 7 and does not destabilize the lipid bilayer. This pH-
dependent effect of PrP structure (see Fig. 7.3 ) in the lipid environment does indicate
the importance of the charge condition in the cellular environment in inducing the
prion effects, that is, induction of prion-related disorder or protein misfolding. In
cancerous cells, it is evident that the cellular exterior and interior across the lipid
membrane experience different pH conditions. The pH dependence of PrP struc-
tures may, therefore, suggest that the prion effects in inducing protein disorders or
misfoldings may depend on the localized charge environment as well.
Investigations have recently been made in order to understand how the morphology
and mechanism of the growth of prion aggregates in membranes are influenced by
lipid composition [ 37 ]. Here, the prion aggregation is observed in both zwitterionic
and anionic membranes, and the morphology of the aggregates formed is dependent
α
 
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