Exploring the binding diversity of intrinsically disordered proteins involved in one-to-many binding

Wei Lun Hsu, Christopher J. Oldfield, Bin Xue, Jingwei Meng, Fei Huang, Pedro Romero, Vladimir N. Uversky, A. Dunker

Research output: Contribution to journalArticle

92 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)258-273
Number of pages16
JournalProtein Science
Volume22
Issue number3
DOIs
StatePublished - Mar 2013

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Intrinsically Disordered Proteins
Molecular recognition
Alternative Splicing
Post Translational Protein Processing
Proteins
Protein Interaction Maps
Databases
Torsional stress
Surface treatment

Keywords

  • Binding site
  • Hub protein
  • Intrinsically disordered protein
  • Linear motif
  • Molecular recognition feature
  • MoRF
  • Protein-protein interaction

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Exploring the binding diversity of intrinsically disordered proteins involved in one-to-many binding. / Hsu, Wei Lun; Oldfield, Christopher J.; Xue, Bin; Meng, Jingwei; Huang, Fei; Romero, Pedro; Uversky, Vladimir N.; Dunker, A.

In: Protein Science, Vol. 22, No. 3, 03.2013, p. 258-273.

Research output: Contribution to journalArticle

Hsu, WL, Oldfield, CJ, Xue, B, Meng, J, Huang, F, Romero, P, Uversky, VN & Dunker, A 2013, 'Exploring the binding diversity of intrinsically disordered proteins involved in one-to-many binding', Protein Science, vol. 22, no. 3, pp. 258-273. https://doi.org/10.1002/pro.2207
Hsu, Wei Lun ; Oldfield, Christopher J. ; Xue, Bin ; Meng, Jingwei ; Huang, Fei ; Romero, Pedro ; Uversky, Vladimir N. ; Dunker, A. / Exploring the binding diversity of intrinsically disordered proteins involved in one-to-many binding. In: Protein Science. 2013 ; Vol. 22, No. 3. pp. 258-273.
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