The assembly of intermediate filaments is a fundamental property of the central rod domain of the individual subunit proteins. This rod domain, with its high propensity for a-helix formation, is the common and identifying feature of this Family of proteins. Assembly occurs in vitro in the absence of other proteins or exogenous sources of energy; in vivo, it appears as if other factors, as yet poorly understood, modulate the assembly of intermediate filaments. Parallel, in-register dimers form via coiled-coil interactions of the rod domain. Tetramers may form from staggered arrays of parallel or antiparallel arrangements of dimers. Higher-order polymerization, which occurs spontaneously if the ionic strength of a mixture of dimers and tetramers is raised, proceeds rapidly through poorly described intermediates to the final 10 nm filament. This process is dependent on and modulated by the non-a-helical end domains, as well as those amino acids present at the very beginning and end of the rod domain. The interactions governing tetramer formation are most probably the same ones that are responsible for the lateral and longitudinal associations within intermediate filaments.
ily responsible for determining the unique characteristics of the individual subunit proteins. In contrast, the central rod domain is highly invariant in its amino acid sequence, especially at thc beginning and end: within membcrs of a single class, the sequence homology is about 70%, while even between classes the homology remains quite high at about 30-50%"32). This feature is the reason why the members of this large group of distinct proleins all polymerize into a common higher order structure: the 10 nm filament. While this point has rcccived little experimental attention, it also implies that the major determinants limiting the extent or degree of polymerization 10 the 10 nm filament are also fundamental properties of the rod domain.
Within any one tissue or cell type, the number of IF pro-A Head --l R o d = y -a Tail 1A 18