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Targeting Intrinsically Disordered Proteins through Dynamic Interactions
Open AccessArticle

Sequence-Dependent Correlated Segments in the Intrinsically Disordered Region of ChiZ

by Alan Hicks 1,2,3,†, Cristian A. Escobar 1,3,4,†, Timothy A. Cross 1,3,4,* and Huan-Xiang Zhou 5,6,*
1
Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA
2
Department of Physics, Florida State University, Tallahassee, FL 32306, USA
3
National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32310, USA
4
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA
5
Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA
6
Department of Physics, University of Illinois at Chicago, Chicago, IL 60607, USA
*
Authors to whom correspondence should be addressed.
These authors contribute equally to this work.
Biomolecules 2020, 10(6), 946; https://doi.org/10.3390/biom10060946
Received: 2 June 2020 / Revised: 17 June 2020 / Accepted: 18 June 2020 / Published: 23 June 2020
(This article belongs to the Special Issue Computational Perspectives on Intrinsic Disorder-Based Functionality)
How sequences of intrinsically disordered proteins (IDPs) code for their conformational dynamics is poorly understood. Here, we combined NMR spectroscopy, small-angle X-ray scattering (SAXS), and molecular dynamics (MD) simulations to characterize the conformations and dynamics of ChiZ1-64. MD simulations, first validated by SAXS and secondary chemical shift data, found scant α-helices or β-strands but a considerable propensity for polyproline II (PPII) torsion angles. Importantly, several blocks of residues (e.g., 11–29) emerge as “correlated segments”, identified by their frequent formation of PPII stretches, salt bridges, cation-π interactions, and sidechain-backbone hydrogen bonds. NMR relaxation experiments showed non-uniform transverse relaxation rates (R2s) and nuclear Overhauser enhancements (NOEs) along the sequence (e.g., high R2s and NOEs for residues 11–14 and 23–28). MD simulations further revealed that the extent of segmental correlation is sequence-dependent; segments where internal interactions are more prevalent manifest elevated “collective” motions on the 5–10 ns timescale and suppressed local motions on the sub-ns timescale. Amide proton exchange rates provides corroboration, with residues in the most correlated segment exhibiting the highest protection factors. We propose the correlated segment as a defining feature for the conformations and dynamics of IDPs. View Full-Text
Keywords: correlated segment; conformational dynamics; intrinsically disordered protein; molecular dynamics; nuclear magnetic resonance (NMR); protein conformation; small-angle X-ray scattering (SAXS) correlated segment; conformational dynamics; intrinsically disordered protein; molecular dynamics; nuclear magnetic resonance (NMR); protein conformation; small-angle X-ray scattering (SAXS)
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MDPI and ACS Style

Hicks, A.; Escobar, C.A.; Cross, T.A.; Zhou, H.-X. Sequence-Dependent Correlated Segments in the Intrinsically Disordered Region of ChiZ. Biomolecules 2020, 10, 946.

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