Exploring The Binding Diversity of Intrinsically Disordered Proteins Involved in One-to-many Binding
Document Type
Article
Publication Date
2013
Keywords
Molecular Recognition Feature, Morf, Linear Motif, Hub Protein, Binding Site, Protein–protein Interaction, Intrinsically Disordered Protein
Digital Object Identifier (DOI)
https://doi.org/10.1002%2Fpro.2207
Abstract
Molecular recognition features (MoRFs) are intrinsically disordered protein regions that bind to partners via disorder-to-order transitions. In one-to-many binding, a single MoRF binds to two or more different partners individually. MoRF-based one-to-many protein–protein interaction (PPI) examples were collected from the Protein Data Bank, yielding 23 MoRFs bound to 2–9 partners, with all pairs of same-MoRF partners having less than 25% sequence identity. Of these, 8 MoRFs were bound to 2–9 partners having completely different folds, whereas 15 MoRFs were bound to 2–5 partners having the same folds but with low sequence identities. For both types of partner variation, backbone and side chain torsion angle rotations were used to bring about the conformational changes needed to enable close fits between a single MoRF and distinct partners. Alternative splicing events (ASEs) and posttranslational modifications (PTMs) were also found to contribute to distinct partner binding. Because ASEs and PTMs both commonly occur in disordered regions, and because both ASEs and PTMs are often tissue-specific, these data suggest that MoRFs, ASEs, and PTMs may collaborate to alter PPI networks in different cell types. These data enlarge the set of carefully studied MoRFs that use inherent flexibility and that also use ASE-based and/or PTM-based surface modifications to enable the same disordered segment to selectively associate with two or more partners. The small number of residues involved in MoRFs and in their modifications by ASEs or PTMs may simplify the evolvability of signaling network diversity.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Protein Science, v. 22, issue 3, p. 258-273
Scholar Commons Citation
Hsu, Wei-Lun; Oldfield, Christopher J.; Xue, Bin; Meng, Jingwei; Huang, Fei; Romero, Pedro; Uversky, Vladimir N.; and Dunker, A. Keith, "Exploring The Binding Diversity of Intrinsically Disordered Proteins Involved in One-to-many Binding" (2013). Molecular Medicine Faculty Publications. 519.
https://digitalcommons.usf.edu/mme_facpub/519
