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J Mol Biol. 2014 Jan 9;426(1):21-35. doi: 10.1016/j.jmb.2013.08.027. Epub 2013 Sep 17.

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

Author information

1
University of Cambridge Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK; Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2
University of Cambridge Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK.
3
Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
4
University of Cambridge Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK. Electronic address: jc162@cam.ac.uk.

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.

KEYWORDS:

GdmCl; IDP; ITC; NIH; National Institutes of Health; guanidinium chloride; intrinsically disordered protein; isothermal titration calorimetry; natively unfolded protein; protein engineering; protein folding; Φ-value analysis

PMID:
24055379
DOI:
10.1016/j.jmb.2013.08.027
[Indexed for MEDLINE]
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