Related ArticlesStructure and dynamics of an intrinsically disordered protein region that partially folds upon binding by chemical-exchange NMR.
J Am Chem Soc. 2017 Aug 07;:
Authors: Charlier C, Bouvignies G, Pelupessy P, Walrant A, Marquant R, Kozlov M, De Ioannes P, Bolik-Coulon N, Sagan S, Cortes P, Aggarwal AK, Carlier L, Ferrage F
Abstract
Many intrinsically disordered proteins (IDPs) and protein regions (IDRs) engage in transient, yet specific, interactions with a variety of protein partners. Often, if not always, interactions with a protein partner lead to partial folding of the IDR. Characterizing the conformational space of such complexes is challenging: in solution-state NMR, signals of the IDR in the interacting region become broad, weak and often invisible; while X-ray crystallography only provides information on fully ordered regions. There is thus a need for a simple method to characterize both fully and partially ordered regions in the bound state of IDPs. Here, we introduce an approach based on monitoring chemical exchange by NMR to investigate the state of an IDR that folds upon binding through the observation of the free state of the protein. Structural constraints for the bound state are obtained from chemical shifts and site-specific dynamics of the bound state are characterized by relaxation rates. The conformation of the interacting part of the IDR was determined and subsequently docked onto the structure of the folded partner. We apply the method to investigate the interaction between the disordered C-terminal region of Artemis and the DNA binding domain of Ligase IV. We show that we can accurately reproduce the structure of the core of the complex determined by X-ray crystallography and identify a broader interface. The method is widely applicable to the biophysical investigation of complexes of disordered proteins and folded proteins.
PMID: 28780862 [PubMed - as supplied by publisher]
Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water
From The DNP-NMR Blog:
Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water
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Kurzbach, D., et al., Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water. Angew. Chem. Int. Ed., 2017. 56(1): p. 389-392.
http://dx.doi.org/10.1002/anie.201608903
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02-28-2017 12:02 AM
[NMR paper] Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water
Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water
Hyperpolarized water can selectively enhance NMR signals of rapidly exchanging protons in osteopontin (OPN), a metastasis-associated intrinsically disordered protein (IDP), at near-physiological pH and temperature. The transfer of magnetization from hyperpolarized water is limited to solvent-exposed residues and therefore selectively enhances signals in 1H-15N correlation spectra. Binding to the polysaccharide heparin was found to induce the unfolding of preformed structural elements in OPN.A...
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12-05-2016 01:06 PM
[NMR paper] Characterization of the conformational preference and dynamics of the intrinsically disordered N-terminal region of beclin 1 by NMR spectroscopy.
Characterization of the conformational preference and dynamics of the intrinsically disordered N-terminal region of beclin 1 by NMR spectroscopy.
Related Articles Characterization of the conformational preference and dynamics of the intrinsically disordered N-terminal region of beclin 1 by NMR spectroscopy.
Biochim Biophys Acta. 2016 Jun 8;
Authors: Yao S, Lee EF, Pettikiriarachchi A, Evangelista M, Keizer DW, Fairlie WD
Abstract
Beclin 1 is a 450 amino acid protein that plays critical roles in the early stages of autophagosome...
Correlation of chemical shifts predicted by molecular dynamics simulations for partially disordered proteins
Correlation of chemical shifts predicted by molecular dynamics simulations for partially disordered proteins
Abstract
There has been a longstanding interest in being able to accurately predict NMR chemical shifts from structural data. Recent studies have focused on using molecular dynamics (MD) simulation data as input for improved prediction. Here we examine the accuracy of chemical shift prediction for intein systems, which have regions of intrinsic disorder. We find that using MD simulation data as input for chemical shift prediction does not...
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11-21-2014 09:04 PM
[NMR paper] Fast hydrogen exchange affects (15)N relaxation measurements in intrinsically disordered proteins.
Fast hydrogen exchange affects (15)N relaxation measurements in intrinsically disordered proteins.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles Fast hydrogen exchange affects (15)N relaxation measurements in intrinsically disordered proteins.
J Biomol NMR. 2013 Jan 12;
Authors: Kim S, Wu KP, Baum J
Abstract
Unprotected amide protons can undergo fast hydrogen exchange (HX) with protons from the solvent. Generally, NMR experiments using the out-and-back...
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02-03-2013 10:22 AM
Quantitative Analysisof Multisite Protein–LigandInteractions by NMR: Binding of Intrinsically Disordered p53 TransactivationSubdomains with the TAZ2 Domain of CBP
Quantitative Analysisof Multisite Protein–LigandInteractions by NMR: Binding of Intrinsically Disordered p53 TransactivationSubdomains with the TAZ2 Domain of CBP
Munehito Arai, Josephine C. Ferreon and Peter E. Wright
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja209936u/aop/images/medium/ja-2011-09936u_0012.gif
Journal of the American Chemical Society
DOI: 10.1021/ja209936u
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/ak4BxkITHl8