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

Towards A Unified Description of Intrinsically Disordered Protein Dynamics under Physiological Conditions using NMR Spectroscopy

Not scheduled
4h
Harnack House and Henry Ford Building

Harnack House and Henry Ford Building

Board: 4
Poster Posters

Speaker

Mr Wiktor Adamski (Groupe Flexibilité et Dynamique des Protéines par RMN, Institut de Biologie Structurale (IBS), CEA, CNRS, University Grenoble Alpes, Grenoble, France)

Description

While intrinsically disordered proteins (IDPs) constitute about half of the human proteome, molecular models of their functional behavior in vivo remain elusive. As proteins of this class do not possess a stable, three-dimensional structure, but sample ensembles of diverse conformations on rather flat energy landscapes, their function is inherently linked to their dynamics occurring on multiple timescales. Recently, we used temperature-dependent $^{15}$N spin relaxation to reveal the physical origin of IDPs backbone motions in the ps-ns range. In our model three dominant dynamic modes are relaxation active: fast librational motions, conformational sampling of backbone dihedral angles and slower chain-like segmental dynamics [1, 2]. Herein, we extend the temperature-dependent model-free analysis by systematically modifying viscosity and, consequently, $^{15}$N spin relaxation rates, to probe the differential effect of molecular environment on the three identified dynamic modes. We carry out our study on two IDPs with remarkably different dynamic properties: the C-terminal domain of Sendai Virus nucleoprotein, which feature a transiently populated helical recognition motif, and the disordered domain of the cancer-associated mitogen-activated protein kinase kinase (MKK4), which is devoid of any secondary structure. Our results suggest that the effects of temperature and viscosity on dynamics can be combined to develop a unified description of the effect of molecular environment parameters on IDP dynamics. In fact, the proposed model is able to predict molecular environment-induced effects on dynamic modes probed by $^{15}$N spin relaxation rates in vitro and in vivo with remarkable accuracy. Overall, we expect that the model will shed some light onto the complex dynamics of IDPs engaged in dynamic complexes in a diverse range of molecular environments.

Literature:
[1] Abyzov A., et al., JACS 2016, 138, 6240 – 6251
[2] Salvi N., et al., Angew. Chem. Int. Ed. 2017, 56, 14020

Primary authors

Mr Wiktor Adamski (Groupe Flexibilité et Dynamique des Protéines par RMN, Institut de Biologie Structurale (IBS), CEA, CNRS, University Grenoble Alpes, Grenoble, France) Dr Sigrid Milles (Groupe Flexibilité et Dynamique des Protéines par RMN, Institut de Biologie Structurale (IBS), CEA, CNRS, University Grenoble Alpes, Grenoble, France) Ms Justine Magnat (Groupe Channels, Institut de Biologie Structurale (IBS), CEA, CNRS, University Grenoble Alpes, Grenoble, France ) Mr Damien Maurin (Groupe Flexibilité et Dynamique des Protéines par RMN, Institut de Biologie Structurale (IBS), CEA, CNRS, University Grenoble Alpes, Grenoble, France) Dr Malene Ringkjobing Jensen (Groupe Flexibilité et Dynamique des Protéines par RMN, Institut de Biologie Structurale (IBS), CEA, CNRS, University Grenoble Alpes, Grenoble, France) Dr Christophe Moreau (Groupe Channels, Institut de Biologie Structurale (IBS), CEA, CNRS, University Grenoble Alpes, Grenoble, France ) Dr Nicola Salvi (Groupe Flexibilité et Dynamique des Protéines par RMN, Institut de Biologie Structurale (IBS), CEA, CNRS, University Grenoble Alpes, Grenoble, France) Dr Martin Blackledge (Groupe Flexibilité et Dynamique des Protéines par RMN, Institut de Biologie Structurale (IBS), CEA, CNRS, University Grenoble Alpes, Grenoble, France)

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