The prion protein (PrP<
SUP>C) i
s a
glycoprotein that in mammal
s, differently from avian
s, can lead to prion di
sea
se
s,by mi
sfoldin
g into a
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ge
s/
gifchar
s/beta2.
gif" BORDER=0 ALIGN="middle">-
sheet-rich patho
genic i
soform (PrP
Sc). Mammal and avian protein
s show differentN-terminal tandem repeat
s: PHGGGWGQ and PHNPGY, both containin
g hi
stidine, wherea
s tyro
sine i
sincluded only in the primary
sequence of the avian protein. Here, by mean
s of potentiometric, circular dichroi
sm(CD), and molecular dynamic
s (MD)
studie
s at different pH value
s, we have inve
sti
gated the conformationof the avian tetrahexarepeat (PHNPGY)
4 (TetraHexaPY) with both N- and C-termini blocked by acetylationand amidation, re
spectively. We have found, al
so with the help of a recently propo
sed protein chirality indicator(Pietropaolo, A.; Muccioli, L.; Berardi, R.; Zannoni, C.
Proteins 2008,
70, 667-677), a conformationaldependence on the protonation
state
s of hi
stidine and tyro
sine re
sidue
s: the turn formation i
s pH driven, andat phy
siolo
gical pH a pivotal role i
s played by the tyro
sine OH
group
s which
give ri
se to a very compact bent
structure of backbone upon formin
g a hydro
gen-bond network.