Interdomain interactions of spectrin are critical for maintenance of the erythrocyte cytoskeleton. In particular, "head-to-head" dimerization occurs when the intrinsically disordered C-terminal tail of β-spectrin binds the N-terminal tail of α-spectrin, folding to form the "spectrin tetramer domain". This non-covalent three-helix bundle domain is homologous in structure and sequence to previously studied spectrin domains. We find that this tetramer domain is surprisingly kinetically stable. Using a protein engineering Φ-value analysis to probe the mechanism of formation of this tetramer domain, we infer that the domain folds by the docking of the intrinsically disordered β-spectrin tail onto the more structured α-spectrin tail. © 2013 The Authors.
Hill, S. A., Kwa, L. G., Shammas, S. L., Lee, J. C., & Clarke, J. (2014). Mechanism of assembly of the non-covalent spectrin tetramerization domain from intrinsically disordered partners. Journal of Molecular Biology, 426(1), 21–35. https://doi.org/10.1016/j.jmb.2013.08.027