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Heterogeneous dynamics in partially disordered proteins

DOI: 10.1039/D0CP03473H DOI Help

Authors: Salla I. Virtanen (University of Helsinki) , Anne M. Kiirikki (University of Helsinki) , Kornelia M. Mikula (University of Helsinki) , Hideo Iwaï (University of Helsinki) , O. H. Samuli Ollila (University of Helsinki)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Physical Chemistry Chemical Physics , VOL 337

State: Published (Approved)
Published: September 2020
Diamond Proposal Number(s): 19951

Open Access Open Access

Abstract: Importance of disordered protein regions is increasingly recognized in biology, but their characterization remains challenging due to the lack of suitable experimental and theoretical methods. NMR experiments can detect multiple timescale dynamics and structural details of disordered protein regions, but their detailed interpretation is often difficult. Here we combine protein backbone 15N spin relaxation data with molecular dynamics (MD) simulations to detect not only heterogeneous dynamics of large partially disordered proteins but also their conformational ensembles. We observed that the rotational dynamics of folded regions in partially disordered proteins is dominated by similar rigid body rotation as in globular proteins, thereby being largely independent of flexible disordered linkers. Disordered regions, on the other hand, exhibit complex rotational motions with multiple timescales below ∼30 ns which are difficult to detect from experimental data alone, but can be captured by MD simulations. Combining MD simulations and backbone 15N spin relaxation data, measured applying segmental isotopic labeling with salt-inducible split intein, we resolved the conformational ensemble and dynamics of partially disordered periplasmic domain of TonB protein from Helicobacter pylori containing 250 residues. To demonstrate the universality of our approach, it was applied also to the partially disordered region of chicken Engrailed 2. Our results pave the way in understanding how TonB transfers energy from inner membrane to the outer membrane receptors in Gram-negative bacteria, as well as the function of other proteins with disordered domains.

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: B21-High Throughput SAXS