Vk. Mishra et Mn. Palgunachari, INTERACTION OF MODEL CLASS-A(1), CLASS-A(2) AND CLASS-Y AMPHIPATHIC HELICAL PEPTIDES WITH MEMBRANES, Biochemistry, 35(34), 1996, pp. 11210-11220
To test the hypothesis that differences in the lipid affinity of excha
ngeable apolipoproteins are due to the presence of different classes o
f amphipathic alpha-helical motifs which differ primarily in the distr
ibution of charged amino acid residues, we designed and synthesized mo
del peptides mimicking class A(1), class A(2), and class Y amphipathic
helices present in these apolipoproteins. Both class A(1) and class A
(2) helices have positive residues at the polar-nonpolar interface and
negative residues at the center of the polar face. However, clusterin
g of positive and negative residues is less exact in class A(1) compar
ed to class A(2) helices, The class Y helices have two negative residu
e clusters on the polar face separating the two arms and the base of t
he Y motif formed by three positive residue clusters, The lipid affini
ties of three 18 residue model peptides representing these; classes, A
c-18A(1)-NH2 (Ac-ELLEKWKEALAALKEALK-NH2), Ac-18A(2)-NH2 (Ac-ELLEKWKEAL
AALAEKLK-NH2), and Ac-18(1)-NH2 (Ac-ELLEKWKEALAALAEKLK-NH2), were dete
rmined by right-angle light scattering, circular dichroism spectroscop
y, differential scanning calorimetry, and fluorescence spectroscopy, T
he observed rank order of lipid affinity of these three peptides is: A
c-18A(2)-NH2 > Ac-18Y-NH2 > Ac-18A(1)-NH2. This order is consistent wi
th the known lipid affinity of exchangeable apolipoproteins containing
class A(1), class A(2), and class Y helices (class A(2) > class Y > c
lass A(1)), Results of this study illustrate the important role of int
erfacial lysine residues in modulating the lipid affinity of amphipath
ic helices and suggest that the effect of interfacial lysine residues
in increasing lipid affinity is additive. We propose that interfacial
lysine residues, in addition to widening the hydrophobic face because
of snorkeling, also help anchor the amphipathic helix in the lipid bil
ayer.