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Extreme disorder in an ultrahigh-affinity protein complex.
- Source :
-
Nature [Nature] 2018 Mar 01; Vol. 555 (7694), pp. 61-66. Date of Electronic Publication: 2018 Feb 21. - Publication Year :
- 2018
-
Abstract
- Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.
- Subjects :
- Binding Sites
Humans
Protein Binding
Static Electricity
Thymosin chemistry
Thymosin metabolism
Histones chemistry
Histones metabolism
Intrinsically Disordered Proteins chemistry
Intrinsically Disordered Proteins metabolism
Protein Precursors chemistry
Protein Precursors metabolism
Thymosin analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 555
- Issue :
- 7694
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 29466338
- Full Text :
- https://doi.org/10.1038/nature25762