Structural basis of the specific protein-protein interactions underlying IF assem

Northwestern University At Chicago, Evanston IL

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Abstract

As indicated in the overview section of this PPG, vimentin consists of a central rod domain flanked by nona-helical head and tail domains. The central rod domain reveals a pronounced seven-residue periodicity, (abcdefg)n, in the distribution of apolar residues. Within this repeat, positions a and d are preferentially occupied by small apolar residues like Leu, lie. Met or Val, typical for a so-called coiled-coil structure (1). A coiled coil is formed by two or more a-helices wound around each other in a 'superhelix', and is a widespread structural motif in proteins (2, 3). This common structural motif enables IF proteins to self-assemble into 10-nm filaments in vitro In the absence of any auxiliary proteins or factors. These filaments are rope-like assemblies made from two to six 4.5-nm protofibrils (i.e., containing eight IF polypeptides each) which, in turn, are made of two intertwined 3-nm protofilaments each (4, 5). Although the molecular architecture of the 3-nm protofilament has not yet been precisely defined, it appears to be made from two antiparallel IF dimers, the latter being 2-stranded a-helical coiled-coils (i.e., formed via the central rod domain) of two parallel, in-register IF polypeptides (also see Figure 6).