An, X. and Guo, X. and Zhang, X. and Baines, A.J. and Debnath, G. and Moyo, D. and Salomao, M. and Bhasin, N. and Johnson, C. and Discher, D. and Gratzer, W.B. and Mohandas, N. (2006) Conformational stabilities of the structural repeats of erythroid spectrin and their functional implications. The Journal of biological chemistry, 281 (15). pp. 10527-10532. ISSN 0021-9258. (The full text of this publication is not available from this repository)
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The two polypeptide chains of the erythroid spectrin heterodimer contain between them 36 structural repeating modules, which can function as independently folding units. We have expressed all 36 and determined their thermal stabilities. These vary widely, with unfolding transition mid-points (T(m)) ranging from 21 to 72 degrees C. Eight of the isolated repeats are largely unfolded at physiological temperature. Constructs comprising two or more adjacent repeats show inter-repeat coupling with coupling free energies of several kcal mol(-1). Constructs comprising five successive repeats from the beta-chain displayed cooperativity and strong temperature dependence in forced unfolding by atomic force microscopy. Analysis of aligned sequences and molecular modeling suggests that high stability is conferred by large hydrophobic side chains at position e of the heptad hydrophobic repeats in the first helix of the three-helix bundle that makes up each repeat. This inference was borne out by the properties of mutants in which the critical residues have been replaced. The marginal stability of the tertiary structure at several points in the spectrin chains is moderated by energetic coupling with adjoining structural elements but may be expected to permit adaptation of the membrane to the large distortions that the red cell experiences in the circulation.
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences > Cell & Developmental Biology Group|
|Depositing User:||Anthony Baines|
|Date Deposited:||05 Sep 2008 06:14|
|Last Modified:||12 Jun 2012 09:52|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/8627 (The current URI for this page, for reference purposes)|