Disordered Motifs and Domains in Cell Control
Tuesday Speaker Abstracts
Role of Functional Disorder in Large Protein Complexes
H. Jane Dyson
1
, Shih-Che Sue
1,2
, Sulakshana Mukherjee
1
.
1
Scripps Research Institute, La Jolla, CA, USA,
2
National Tsing Hua University, Hsinchu,
Taiwan.
The eukaryotic proteome contains proteins that populate a wide variety of structural forms. Fully
folded proteins are the most familiar from structural studies, but disordered and partly folded
forms are also functional. Some proteins and protein domains are completely disordered, and this
disorder is required for their correct function. Cellular signaling is one area where a number of
functional disordered and partly ordered proteins play a part. We have been exploring the role of
disorder in the interactions of the transcription factor NFκB with its inhibitor protein IκBα by
measuring NMR spectra of component domains of these proteins. Disorder and partial order in
IκBα contribute to the affinity and specificity of its interaction with NFκB, particularly in its
competition for DNA-bound NFκB. Disorder and partial order are also observed in NFκB,
adding to the complexity of its interactions with both IκBα and DNA. These studies illustrate the
role of flexibility in the interactions of polypeptide chains as they interact to perform their
functions.
- 39 -
