Influence of the C-terminus of the glycophorin A transmembrane fragment onthe dimerization process

The monomer-dimer equilibrium of the glycophorin A (GpA) transmembrane (TM) fragment has been used as a model system to investigate the amino acid seq uence requirements that permit an appropriate helix-helix packing in a memb rane-mimetic environment. In particular, we have focused on a region of the helix where no crucial residues for packing have been yet reported. Variou s deletion and replacement mutants in the C-terminal region of the TM fragm ent showed that the distance between the dimerization motif and the flankin g charged residues from the cytoplasmic side of the protein Is important fo r helix packing. Furthermore, selected GpA mutants have been used to illust rate the rearrangement of TM fragments that takes place when leucine repeat s are introduced in such protein segments. We also show that secondary stru cture of GpA derivatives was independent from dimerization, in agreement wi th the two-stage model for membrane protein folding and oligomerization.