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.
- 62 -
