Disordered Motifs and Domains in Cell Control
Sunday Speaker Abstracts
Close Encounters of the Third Kind: Disordered Binding Domains
A. Keith Dunker
, Christopher J. Oldfield, Fei Huang, and Jianhong Zhou
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine,
Indianapolis, Indiana
While developing intrinsically disordered protein (IDP) predictors (1), we noticed that our
training set proteins contained several examples for which false positive predictions of structure
exhibited strong overlap with binding sites for protein partners (2). We called such sites
molecular recognition features (MoRFs) (3) and we developed a collection of MoRF predictors
(4-6). In the selected examples, MoRFs were rather short, typically less than 15 residues in
length. In parallel studies we identified longer partner-binding disordered regions that we called
disordered binding domains, several of which matched hidden Markov models called Pfams (7).
Thus, we studied Pfams that are predicted to be disordered (8). We will present our in-progress
work on predicted-to-be disordered Pfams that, contrary to the IDP predictions, are found to be
structured in the Protein Data Bank.
(1) Romero, P., Obradovic, Z., Kissinger, K., Villafranca, J.E., and Dunker, A.K. Identifying
disordered regions in proteins from amino acid sequence. Int. Conf. Neural Networks 1:90-
95 (1997).
(2) Garner, E., Romero, P., Dunker, A.K., and Obradovic, Z. Predicting binding regions within
disordered proteins. Genome Informatics 10:41-50 (1999)
(3) Mohan A., Radivojac P., Oldfield C.J., Vacic V., Cortese M.S., Dunker A.K., Uversky V.N.
Analysis of molecular recognition features (MoRFs). J. Mol. Biol. 362: 1043-1059 (2006)
(4) Oldfield, C.J., Chen, Y., Cortese, M.C., Romero, P.R., Uversky, V.N., Dunker, A.K. Coupled
binding and folding with alpha-helical molecular recognition elements. Biochemistry 44:
12454-12470 (2005)
(5) Cheng, Y., Oldfield, C.J., Meng, J., Romero, P., Uversky, V.N., and Dunker, A.K. Mining -
helix-forming molecular recognition features (
α
-MoRFs) with cross-species sequence
alignments. Biochemistry 46: 13468-13477 (2007).
(6) Disfani, F.M., Hsu, W.L., Mizianty, M., Oldfield, C., Xue, B., Dunker, A.K., Uversky, V.N.,
Kurgan, K. MoRFpred, a computational tool for sequence-based prediction and
characterization of disorder-to-order transition binding sites in proteins. Bioinformatics
28:i75-i83 (2012)
(7) Tompa, P., Fuxreiter, M., Oldfield, C.J., Simon, I., Dunker, A.K., and Uversky, V.N. Close
encounters of the third kind: disordered domains and the interactions of proteins. Bioessays
31: 328-335 (2009)
(8) Williams, R.W., Xue, B., Uversky, V.N., and Dunker, A.K. Distribution and cluster analysis
of predicted intrinsically disordered proteins Pfam domains. Intrins. Disord. Prot. 1:e25724
(2013)
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