Helix Helix Interactions In Reconstituted High-Density-Lipoproteins

In this work we calculated the ionic interactions between adjacent amphipathic
helices of apo A-I and apo A-IV. The calculation of the electrostatic potential
around the helices helps identify the charged residues susceptible to form salt
bridges between adjacent helices. An estimation of the stability of the different
pairs of helices is derived from the calculation of the energy of interaction
between contiguous helices at a water/lipid interface after energy minimization.
The most stable energetic conformation corresponds to the 17-residue helices
oriented anti-parallel and separated by a stretch of 5 residues in an extended
beta-strand conformation, as calculated through the 'stereo alphabet' calculation
procedure. In a pair of helices, the hydrophobic faces are directed towards the
lipid core of the discoidal phospholipid-apolipoprotein complex and the
hydrophobic lipid-protein interactions are major determinants for the stability
of the complex. Interactions between polar residues located on the opposite face
of the helix and water molecules can also contribute to the overall energy of the
system. Finally, salt bridge formation between residues of opposite charge along
the edge of the helical segments contribute to the cooperativity of the
phospholipid-apolipoprotein complex formation. The mode of assembly of the
amphipathic helical repeats of the apolipoproteins around the edge of a discoidal
complex is therefore determined both by the hydrophobic character of the residues
and by the charge complementarity along the edge of the helices which increases
the structural stability and determines the relative orientation of the
helices.