Biophysical studies of membrane proteins/peptides. Interaction with ...

Chapter V – Interaction of Helix‐0 of the N‐BAR Domain
With Lipid Membranes
The membrane modelling properties of N-BAR domains are generally attributed to
two structural features of the BAR domain containing proteins: the concave surface of
the crescent shaped dimer, that is expected to act as a scaffold for curvature and an N-
terminal amphipatic helix or H0, that is expected to be deeply buried within the lipid
bilayer, driving monolayer asymmetry and finally curvature. This latter strategy for
curvature generation should be effective in the absence of the rest of the protein, and a
peptide comprising this amphipatic helix would be expected to produce the same
results. The results reproduced here clearly demonstrate that this is not the case. H0 is
unable to drive significant changes in liposome morphology. Therefore we can conclude
that N-BAR domains do not use their N-terminal amphipatic helices to produce bilayer
curvature in the manner often proposed (Gallop and McMahon, 2005; Gallop et al.,
2006; Masuda et al., 2006). Nevertheless, the results point to different roles of Helix-0
on membrane remodelling by N-BAR domains. The high water/lipid partition
coefficients determined for H0 are expected to have a dramatic effect in the partition
properties of the entire protein, and this alone could explain the great decreases in
liposome tubulation efficiency of BAR domains without H0. A role as a mediator of
interactions between dimers of BAR domains was also proposed for H0 (Gallop and
McMahon, 2005), and here it is shown that H0 does indeed oligomerize into dimers in
the lipid environment. Oligomerization of H0 might provide BAR domain-containing
proteins with a more efficient mechanism to colocalize, and membrane curvature
induction by scaffolding by proteins is only expected to be efficient at high local
concentrations of scaffold proteins.
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