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

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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