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Mechanism of assembly of the non-covalent spectrin tetramerization domain from intrinsically disordered partners.

ABSTRACT: 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.

SUBMITTER: Hill SA

PROVIDER: S-EPMC9082959 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Mechanism of assembly of the non-covalent spectrin tetramerization domain from intrinsically disordered partners.

Hill Stephanie A SA Kwa Lee Gyan LG Shammas Sarah L SL Lee Jennifer C JC Clarke Jane J

Journal of molecular biology 20130917 1

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. Usin ...[more]

PMID: 24055379

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