25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Disordered Protein Complexes

26 Aug 2019, 10:30
Lecture Hall A (Henry Ford Building)

Lecture Hall A

Henry Ford Building

Invited talk Biological applications Biomolecules


Prof. Birthe B. Kragelund (University of Copenhagen)


Intrinsically disordered proteins (IDPs) (or –regions (IDRs)) are functional while existing in broad ensembles of near iso-energetic conformations. Despite their lack of structure, IDPs are involved in molecular communication forming associations ranging from binary, discrete complexes to large multicomponent assemblies. Similar to globular proteins their complexes serve structural, functional and regulatory roles, but due to their dynamic nature, they expand the types of association possible, enabling functional regulations by very different mechanisms. The fast dynamics characteristic of IDPs may persist in their complexes to various degrees. We have been exploring the role of disorder in cellular control processes including pH homeostasis, cytokine signalling, transcriptional regulation, and DNA metabolism, combining NMR with other biophysical methods as SAXS, neutron diffraction, single-molecule FRET and cell biology [1–4]. In one end, we observe folding-upon-binding forming nearly globular-like complexes with little disorder while at the other end, disorder may persist and results in complexes where both binding partners stay disordered in high-affinity binding [3]. Still, the kinetics combined with higher order complex formation allows regulation on biologically relevant timescales. Between these extremes, a continuum of dynamic complexes is possible. The characterisation and functional decoding of dynamic complexes challenges the methodological toolbox, but NMR continues to be a critical contributor in the understanding of disorder dependent biology.

1 Bugge, K., et al (2016) A combined computational and structural model of the full-length human prolactin receptor. Nat Comm 7, 11578.
2 Bugge, K., et al. (2018) Structure of Radical-Induced Cell Death1 Hub Domain Reveals a Common αα-Scaffold for Disorder in Transcriptional Networks. Structure 26, 734–746.
3 Borgia, A., et al. (2018) Extreme disorder in an ultrahigh-affinity protein complex. Nature, 555, 61–66.
4 Hendus-Altenburger, R., et al (2016) The human Na(+)/H(+) exchanger 1 is a membrane scaffold protein for extracellular signal-regulated kinase 2. BMC Biol, 14, 31.

Primary author

Prof. Birthe B. Kragelund (University of Copenhagen)

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