Mechanism of Assembly of the Non-Covalent Spectrin Tetramerization Domain from Intrinsically Disordered Partners

JOURNAL OF MOLECULAR BIOLOGY

卷:426

Article

Hill, Stephanie A.^1,2  Kwa, Lee Gyan¹  Shammas, Sarah L.¹  Lee, Jennifer C.²  Clarke, Jane¹ 

[1] Univ Cambridge, Chem Lab, Cambridge CB2 1EW, England

[2] NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA

关键词: protein folding;    protein engineering;    phi-value analysis;    IDP;    natively unfolded protein;   

DOI  :  10.1016/j.jmb.2013.08.027

来源: Elsevier

【 摘 要 】

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 beta-spectrin binds the N-terminal tail of a-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 phi-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 beta-spectrin tail onto the more structured a-spectrin tail. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

【 授权许可】

Free