In membrane proteins, the extent to which polarity, hydrogen bonding, and
van der Waals packing interactions of the buried, internal residues direct
protein folding and association of transmembrane segments is poorly understood.
The energetics associated with these various interactions should differ substantially
between membrane versus water-soluble proteins. To help evaluate these
energetics, we have altered a water-soluble, two-stranded coiled-coil peptide
to render its sequence soluble in membranes. The membrane-soluble peptide
associates in a monomer-dimer-trimer equilibrium, in which the trimer predominates
at the highest peptide/detergent ratios. The oligomers are stabilized by a
buried Asn side chain. Mutation of this Asn to Val essentially eliminates
oligomerization of the membrane-soluble peptide. Thus, within a membrane-like
environment, interactions involving a polar Asn side chain provide a strong
thermodynamic driving force for membrane helix association.
