The importance of intramolecular ion pairing in intermediate filaments ( structure / a - helices / keratin / coiled - coil / ion pairs )


Nuclear and cytoskeletal networks of 10-nm intermediate filaments (IFs) are probably ubiquitous in multicellular eukaryotes. They likely play a role in maintaining the mechanical integrity of a cell. With the exception of the nuclear lamins, IF proteins can form IFs in vitro in the absence of cofactors or associated proteins. Below we present data suggesting that the large a-helical "rod" domains of IF proteins are stabilized by large numbers (up to 50) of intrahelical ion pairs formed by residues of opposite charge situated four residues apart. These many ion pairs, sometimes involving up to 30% of the residues within a coiled-coil IF segment, can potentially contribute as much as 10-25 kcal/mol (1 kcal = 4.18 kJ) to the stability ofa single a-helical rod. Such stabilization is likely to play a major role in the chemical and physical stability of IF networks in vitro and in vivo. An investigation of other coiled-coil proteins shows that selection for intrahelical ion pairing is not simply a property intrinsic to coiled-coil proteins. Rather, there is a correlation between the degree to which there is selection for intrahelical ion pairs and the extent to which a coiled-coil protein participates in highly ordered multimolecular interactions-e.g., as in IFs and myosin thick filaments. The propensity of putative ion pairs in some IF proteins-e.g., epidermal keratins-suggests that an underlying structural stability at the level of the monomer may play an important role in the extraordinary stability of dimers and higher ordered structures in cytoplasmic IFs. Given that intermediate filament (IF) proteins have not been crystallized, knowledge of their common structure has relied heavily on secondary structure predictions from primary sequence data (refs. 1-3; reviewed in refs. 4 and 5). IF proteins are subdivided into five distinct sequence types, all of which have a central 310to 360-amino acid residue, a-helical rod domain interrupted by three short nonhelical linker segments (Fig. 1). The most highly conserved regions of IF proteins are -15 amino acids at each end of the rod. These regions are particularly sensitive to amino acid substitution or deletion (6-10). The a-helical segments of IF rods contain heptad repeats of hydrophobic residues, where a and d of abcdefg sequences are frequently apolar (11). This creates a hydrophobic stripe that provides a surface for the intertwining of two IF polypeptides into a parallel, in-register coiled-coil dimer. This first step in IF polymerization (12, 13) is energetically so favorable for some IF proteins that it is stable even in buffers containing 8 M urea and a reducing agent (14). In solution, dimers align laterally in an antiparallel fashion to form tetramers (15) in staggered and unstaggered (14-23) arrangements. Lateral and longitudinal alignments of "-10,000 tetramers give rise to Head ail

4 Figures and Tables

Cite this paper

@inproceedings{Letai2005TheIO, title={The importance of intramolecular ion pairing in intermediate filaments ( structure / a - helices / keratin / coiled - coil / ion pairs )}, author={Anthony G. Letai}, year={2005} }