Chapter 1 27 With knowledge of the complete amino acid sequences of the starting type-I and type-II proteins and of the parallel in-phase association of these in the α-helical coiled-coil dimers, it was thereby possible for Steinert and his collaborators to establish the relative adjacency of the dimers in the original intermediate filament.62 Three dominant modes of dimer alignment were found in which anti-parallel association of adjacent dimers occurred and a fourth minor parallel association. These are shown in Figure 15, the upper diagram of which illustrates the layout of the 1A, IB, 2A, 2B, L1, L12 and L2 regions in the parallel in-register amalgamation of the type-I and type-II proteins of the coiled-coil dimer. In the A 11 mode the dimers were in anti-parallel staggered alignment with their 1B segments overlapping. In A 22 mode the dimers were anti-parallel and staggered with their 2B segments overlapping whilst in A 12 mode the dimers were again anti-parallel but in register with 1B and 2B segments partially overlapped. In the minor A CN mode the dimers were parallel to each other but with their ends just touching. Arising from the A 11 , A 22 and A 12 anti-parallel and A CN modes of association between coiled-coil dimers determined by the cross-linking experiments, models have been constructed for the possible organization of the 32 protein chains within the keratin intermediate filament.62 The models have been progressively refined Figure 15. The topmost part of this diagram illustrates the segmental organization within a KIF coiled-coil dimer. A 11 , A 22 , A 12 and A CN depict the adjacencies of the dimers within intermediate filaments assembled in vitro from the isolated proteins determined by the chemical cross-linking studies of Steinert and co-workers.62