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Fuzzy regions in an intrinsically disordered protein impair protein-protein interactions
- Source :
- FEBS Journal, FEBS Journal, 2016, 283 (4), pp.576-594. ⟨10.1111/febs.13631⟩, FEBS Journal, Wiley, 2016, 283 (4), pp.576-594. ⟨10.1111/febs.13631⟩
- Publication Year :
- 2016
-
Abstract
- Despite the partial disorder-to-order transition that intrinsically disordered proteins often undergo upon binding to their partners, a considerable amount of residual disorder may be retained in the bound form, resulting in a fuzzy complex. Fuzzy regions flanking molecular recognition elements may enable partner fishing through non-specific, transient contacts, thereby facilitating binding, but may also disfavor binding through various mechanisms. So far, few computational or experimental studies have addressed the effect of fuzzy appendages on partner recognition by intrinsically disordered proteins. In order to shed light onto this issue, we used the interaction between the intrinsically disordered C-terminal domain of the measles virus (MeV) nucleoprotein (NTAIL ) and the X domain (XD) of the viral phosphoprotein as model system. After binding to XD, the N-terminal region of NTAIL remains conspicuously disordered, with α-helical folding taking place only within a short molecular recognition element. To study the effect of the N-terminal fuzzy region on NTAIL /XD binding, we generated N-terminal truncation variants of NTAIL , and assessed their binding abilities towards XD. The results revealed that binding increases with shortening of the N-terminal fuzzy region, with this also being observed with hsp70 (another MeV NTAIL binding partner), and for the homologous NTAIL /XD pairs from the Nipah and Hendra viruses. Finally, similar results were obtained when the MeV NTAIL fuzzy region was replaced with a highly dissimilar artificial disordered sequence, supporting a sequence-independent inhibitory effect of the fuzzy region.
- Subjects :
- 0301 basic medicine
Biology
Intrinsically disordered proteins
Biochemistry
Fuzzy logic
split-GFP
Protein–protein interaction
03 medical and health sciences
Molecular recognition
deletion variants
excluded volume
intrinsically disordered proteins
partner binding
Elméleti orvostudományok
Molecular Biology
ComputingMilieux_MISCELLANEOUS
030102 biochemistry & molecular biology
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
Cell Biology
Orvostudományok
Phosphoproteins
[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
Nucleoprotein
Folding (chemistry)
Intrinsically Disordered Proteins
Crystallography
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
030104 developmental biology
Order (biology)
Nucleoproteins
Measles virus
Phosphoprotein
Biophysics
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 1742464X and 17424658
- Database :
- OpenAIRE
- Journal :
- FEBS Journal, FEBS Journal, 2016, 283 (4), pp.576-594. ⟨10.1111/febs.13631⟩, FEBS Journal, Wiley, 2016, 283 (4), pp.576-594. ⟨10.1111/febs.13631⟩
- Accession number :
- edsair.doi.dedup.....8c425b1c929c59e3768b1ae36e226f2a