Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Poster Session I

11-POS Board 11 Protein Design for Decreased Disorder Elliot D. Drew 1 , David T. Jones 2 , Bonnie A. Wallace 1 . 2 University College London, London, United Kingdom. 1 Birkbeck College, London, United Kingdom, Disorder-to-order transitions are the basis for the promiscuity and diversity of many interactions seen in intrinsically disordered proteins (IDPs), leading to the ubiquity of intrinsic disorder in signalling and regulatory proteins. However, the complexity of IDP dynamics present a unique challenge to the structural characterisation of these proteins. Using the Small Hydrophilic Endoplasmic Reticulum associated Protein (SHERP) from the parasite L. major, protein design principles have been applied to explore the protein’s disorder-to-order transitions both computationally and in vitro. A number of sequences were identified which significantly decrease protein disorder and a strong relationship between decreasing disorder and increasing energetic stability is seen in SHERP mutants. This has allowed for the identification of key residues involved in structural transitions and the design of mutant proteins which preserve key features of the wild-type ordered structure.

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