Duplicated subunits in complexes interact. (a) Interactions between paralogous subunits (red) are more frequent than expected given the stoichiometry of subunits within protein complexes. Chains from PQS complexes were binned according to probability of forming a homomeric interaction or interactions between paralogous or different chains (see Materials and methods). The frequencies at which these chains form homodimers and paralogous dimers (averaged for each bin) are shown as blue and red bars, respectively. In a random scenario, all the points lie within the range shown in the black lines. (b) Possible arrangements of two distinct subunits in a hexameric ring like that of the F1 complex. The actual F1 complex is shown on the left. Bars of different colors correspond to different inter-subunit interfaces. (c) If there are multiple identical and paralogous chains within a protein complex, the chains tend to be arranged in three-dimensional space so that the paralogous chains rather than identical chains are contacting each other, corresponding to the scenario shown on the left. Note that when there is a choice, interactions between paralogous proteins are always preferred. This experiment is similar to that described in (a), but considering only the two types of interaction in the calculations. (d) The role of oligomers of paralogues in generating structural diversity. n is the number of protein complexes found in PQS that have identical chains (left) or paralogous chains (right), which contact the same (top) or distinct binding partners (bottom). Hetero-oligomers that contain paralogous dimers are more frequently asymmetrical (10/31) than those containing homomers (6/210), that is, paralogues tend to bind different partners. The complexes shown illustrate the four possible situations. Top left is the tryptophan synthase from Salmonella typhimurium, in which the homomeric α:α dimer (blue) binds one β subunit on each side (yellow) , which represents symmetry in binding partners of homomers. Top right is the photosynthetic reaction centre from Rhodopseudomonas viridis, in which both paralogous L and M chains (blue and purple) bind to the H and C subunits (shown in yellow) , which illustrates symmetry in the binding partners of a dimer of paralogues. Bottom left is the structure of the Rac1 small GTPase bound to the arfaptin-1 homodimer  from Homo sapiens, in which Rac1 binds solely one of the arfaptin chains, but occupies a volume that excludes the possibility of additional Rab molecules binding the other arfaptin chain; this illustrates the rare cases of asymmetry in the binding partners of homomers. Bottom right is the RNA polymerase from S. cerevisiae , in which many peripheral subunits decorate the central core formed by the dimer of paralogues A:B, which illustrates the creation of asymmetry by the duplication of the ancestral homodimer .