Journal Article

FZJ-2018-01783

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png DNP-Enhanced MAS NMR: A Tool to Snapshot Conformational Ensembles of α -Synuclein in Different States

Uluca, B.FZJ* ; Viennet, T.FZJ* ; Petrović, D.FZJ* ; Shaykhalishahi, H.FZJ* ; Weirich, F.FZJ* ; Gönülalan, A.FZJ* ; Strodel, B.FZJ* ; Etzkorn, M.FZJ* ; Hoyer, W.FZJ* ; Heise, H. (Corresponding author)FZJ*

2018
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: http://hdl.handle.net/2128/18225  doi:10.1016/j.bpj.2018.02.011

Abstract: Intrinsically disordered proteins dynamically sample a wide conformational space and therefore do not adopt a stable and defined three-dimensional conformation. The structural heterogeneity is related to their proper functioning in physiological processes. Knowledge of the conformational ensemble is crucial for a complete comprehension of this kind of proteins. We here present an approach that utilizes dynamic nuclear polarization-enhanced solid-state NMR spectroscopy of sparsely isotope-labeled proteins in frozen solution to take snapshots of the complete structural ensembles by exploiting the inhomogeneously broadened line-shapes. We investigated the intrinsically disordered protein α-synuclein (α-syn), which plays a key role in the etiology of Parkinson’s disease, in three different physiologically relevant states. For the free monomer in frozen solution we could see that the so-called “random coil conformation” consists of α-helical and β-sheet-like conformations, and that secondary chemical shifts of neighboring amino acids tend to be correlated, indicative of frequent formation of secondary structure elements. Based on these results, we could estimate the number of disordered regions in fibrillar α-syn as well as in α-syn bound to membranes in different protein-to-lipid ratios. Our approach thus provides quantitative information on the propensity to sample transient secondary structures in different functional states. Molecular dynamics simulations rationalize the results.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)
2. JARA - HPC (JARA-HPC)

Research Program(s):

1. 551 - Functional Macromolecules and Complexes (POF3-551) (POF3-551)
2. Computational Enzyme Design (jics69_20151101) (jics69_20151101)

Appears in the scientific report 2018

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Database coverage:
; ; ; BIOSIS Previews ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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