IGBMC du CNRS, 1 Rue Laurent Fries Bp 163, Illkirch, 67404, FRANCE bergdoll@titus.u-strasbg.fr
Oligomerization is often necessary for protein activity or regulation and its efficiency is fundamental for the cell. Bacterial resistance against bleomycin is achieved by Bleomycin Resistance Protein dimers. These dimers show exchanged arms which are important for dimerization. The 3D structures of a large number of other oligomers contain protomers tightly anchored to each other by exchanged arms or swapped domains.
Upon examination of these structures, we observe an extremely frequent occurence of one or several prolines at the point where the arm leaves the protomer. Sequence alignment and site-directed mutagenesis confirm the importance of these prolines. Their conservation at these hinge regions is explained by the constraints that they impose on polypeptide main chain conformation and dynamics: by rigidifying the main chain, prolines impede the folding back of the arms onto the molecule.
Prolines can be considered as 'quaternary structure helpers' and this property could be used to engineer synthetic oligomers or to change the ratio monomers/oligomers.