DNP-Enhanced MAS NMR: A Tool to Snapshot Conformational Ensembles of ?-Synuclein in Different States.
Biophys J. 2018 Apr 10;114(7):1614-1623
Authors: Uluca B, Viennet T, Petrovi? D, Shaykhalishahi H, Weirich F, Gönülalan A, Strodel B, Etzkorn M, Hoyer W, Heise H
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 ?-synuclein (?-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 ?-helical and ?-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 ?-syn as well as in ?-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.
[NMR paper] NMR Spectroscopic Studies of the Conformational Ensembles of Intrinsically Disordered Proteins.
NMR Spectroscopic Studies of the Conformational Ensembles of Intrinsically Disordered Proteins.
Related Articles NMR Spectroscopic Studies of the Conformational Ensembles of Intrinsically Disordered Proteins.
Adv Exp Med Biol. 2015;870:149-185
Authors: Kurzbach D, Kontaxis G, Coudevylle N, Konrat R
Abstract
Intrinsically disordered proteins (IDPs) are characterized by substantial conformational flexibility and thus not amenable to conventional structural biology techniques. Given their inherent structural flexibility NMR...
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09-21-2015 03:01 PM
[NMR paper] Further exploration of the conformational space of ?-synuclein fibrils: solid-state NMR assignment of a high-pH polymorph.
Further exploration of the conformational space of ?-synuclein fibrils: solid-state NMR assignment of a high-pH polymorph.
Related Articles Further exploration of the conformational space of ?-synuclein fibrils: solid-state NMR assignment of a high-pH polymorph.
Biomol NMR Assign. 2015 Aug 30;
Authors: Verasdonck J, Bousset L, Gath J, Melki R, Böckmann A, Meier BH
Abstract
Polymorphism is a common and important phenomenon for protein fibrils which has been linked to the appearance of strains in prion and other neurodegenerative...
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09-01-2015 10:48 AM
NMR Studies of Dynamic Biomolecular Conformational Ensembles
NMR Studies of Dynamic Biomolecular Conformational Ensembles
Publication date: Available online 28 November 2014
Source:Progress in Nuclear Magnetic Resonance Spectroscopy</br>
Author(s): Dennis A. Torchia</br>
Multidimensional heteronuclear NMR approaches can provide nearly complete sequential signal assignments of isotopically enriched biomolecules. The availability of assignments together with measurements of spin relaxation rates, residual spin interactions, J-couplings and chemical shifts provides information at atomic resolution about internal dynamics on...
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11-29-2014 04:09 PM
NMR-Based Conformational Ensembles Explain pH-Gated Opening and Closing of OmpG Channel
NMR-Based Conformational Ensembles Explain pH-Gated Opening and Closing of OmpG Channel
Tiandi Zhuang, Christina Chisholm, Min Chen and Lukas K. Tamm
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja408206e/aop/images/medium/ja-2013-08206e_0011.gif
Journal of the American Chemical Society
DOI: 10.1021/ja408206e
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/UcxM_KhEqyU
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[NMR paper] NMR-based Conformational Ensembles Explain pH-Gated Opening and Closing of OmpG Channel.
NMR-based Conformational Ensembles Explain pH-Gated Opening and Closing of OmpG Channel.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles NMR-based Conformational Ensembles Explain pH-Gated Opening and Closing of OmpG Channel.
J Am Chem Soc. 2013 Sep 10;
Authors: Zhuang T, Chisholm C, Chen M, Tamm LK
Abstract
The outer membrane protein G (OmpG) is a monomeric 33 kDa 14-stranded ?-barrel membrane protein functioning as a non-specific porin for the uptake of...
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09-12-2013 11:02 PM
[NMR paper] Conformational Ensembles in GPCR Activation.
Conformational Ensembles in GPCR Activation.
Related Articles Conformational Ensembles in GPCR Activation.
Cell. 2013 Jan 31;152(3):385-6
Authors: Vardy E, Roth BL
Abstract
Recent advances in G-protein-coupled receptor structural biology have provided only limited insight into the active conformations of these key signaling molecules. A paper from Nygaard et*al. reveals the dynamic nature of GPCRs along the activation pathway by complementing NMR experiments with ultralong-timescale molecular dynamics simulations.
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02-05-2013 09:51 PM
PPM: a side-chain and backbone chemical shift predictor for the assessment of protein conformational ensembles
PPM: a side-chain and backbone chemical shift predictor for the assessment of protein conformational ensembles
Abstract The combination of the wide availability of protein backbone and side-chain NMR chemical shifts with advances in understanding of their relationship to protein structure makes these parameters useful for the assessment of structural-dynamic protein models. A new chemical shift predictor (PPM) is introduced, which is solely based on physicalâ??chemical contributions to the chemical shifts for both the protein backbone and methyl-bearing amino-acid side chains. To...
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09-15-2012 09:04 AM
[NMR paper] NMR characterization of partially folded and unfolded conformational ensembles of pro
NMR characterization of partially folded and unfolded conformational ensembles of proteins.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_120x27.gif Related Articles NMR characterization of partially folded and unfolded conformational ensembles of proteins.
Biopolymers. 1999;51(3):191-207
Authors: Barbar E
Studies of unfolded and partially folded proteins provide important insight into the initiation and process of protein folding. This review focuses on the...
DNP-Enhanced MAS NMR: A Tool to Snapshot Conformational Ensembles of ?-Synuclein in Different States.
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