Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein by NMR Exchange Spectroscopy.
J Am Chem Soc. 2017 Dec 25;:
Authors: Delaforge E, Kragelj J, Tengo L, Palencia A, Milles S, Bouvignies G, Salvi N, Blackledge M, Jensen MR
Abstract
Intrinsically disordered proteins (IDPs) display a large number of interaction modes including folding-upon-binding, binding without major structural transitions or binding through highly dynamic, so-called fuzzy, complexes. The vast majority of experimental information about IDP binding modes have been inferred from crystal structures of proteins in complex with short peptides of IDPs. However, crystal structures provide a mainly static view of the complexes and do not give information about the conformational dynamics experienced by the IDP in the bound state. Knowledge of the dynamics of IDP complexes is of fundamental importance in order to understand how IDPs engage in highly specific interactions without concomitantly high binding affinity. Here, we combine rotating-frame R1?, Carr-Purcell-Meiboom Gill (CPMG) relaxation dispersion as well as chemical exchange saturation transfer (CEST) to decipher the dynamic interaction profile of an IDP in complex with its partner. We apply the approach to the dynamic signaling complex formed between the mitogen-activated protein kinase (MAPK) p38? and the intrinsically disordered regulatory domain of the MAPK kinase MKK4. Our study demonstrates that MKK4 employs a subtle combination of interaction modes in order to bind to p38?, leading to a complex displaying significantly different dynamics across the bound regions.
PMID: 29276882 [PubMed - as supplied by publisher]
[NMR paper] The thermodynamic basis of the fuzzy interaction of an intrinsically disordered protein
The thermodynamic basis of the fuzzy interaction of an intrinsically disordered protein
Many intrinsically disordered proteins (IDP) that fold upon binding retain conformational heterogeneity in IDP-target complexes. The thermodynamics of such fuzzy interactions is poorly understood. Here we introduce a thermodynamic framework, based on analysis of ITC and CD spectroscopy data, that provides experimental description of IDP association in terms of folding and binding contributions which can be predicted using sequence folding propensities and molecular modeling. We show how IDP can...
nmrlearner
Journal club
0
09-15-2017 08:41 PM
[NMR paper] Structure and dynamics of an intrinsically disordered protein region that partially folds upon binding by chemical-exchange NMR.
Structure and dynamics of an intrinsically disordered protein region that partially folds upon binding by chemical-exchange NMR.
Related Articles Structure 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...
nmrlearner
Journal club
0
08-07-2017 07:31 PM
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
p.p1 {margin: 0.0px 0.0px 0.0px 36.0px; text-indent: -36.0px; font: 12.0px Helvetica}
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
nmrlearner
News from NMR blogs
0
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...
nmrlearner
Journal club
0
12-05-2016 01:06 PM
[NMR paper] Identification of Dynamic Modes in an Intrinsically Disordered Protein using Temperature-dependent NMR Relaxation.
Identification of Dynamic Modes in an Intrinsically Disordered Protein using Temperature-dependent NMR Relaxation.
Related Articles Identification of Dynamic Modes in an Intrinsically Disordered Protein using Temperature-dependent NMR Relaxation.
J Am Chem Soc. 2016 Apr 26;
Authors: Abyzov A, Salvi N, Schneider R, Maurin D, Ruigrok RW, Jensen MR, Blackledge M
Abstract
[NMR paper] Dynamics of the Intrinsically Disordered C-Terminal Domain of the Nipah Virus Nucleoprotein and Interaction with the X Domain of the Phosphoprotein as Unveiled by NMR Spectroscopy.
Dynamics of the Intrinsically Disordered C-Terminal Domain of the Nipah Virus Nucleoprotein and Interaction with the X Domain of the Phosphoprotein as Unveiled by NMR Spectroscopy.
Related Articles Dynamics of the Intrinsically Disordered C-Terminal Domain of the Nipah Virus Nucleoprotein and Interaction with the X Domain of the Phosphoprotein as Unveiled by NMR Spectroscopy.
Chembiochem. 2014 Dec 9;
Authors: Baronti L, Erales J, Habchi J, Felli IC, Pierattelli R, Longhi S
Abstract
We provide an atomic-resolution description...
nmrlearner
Journal club
0
12-11-2014 11:22 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...
Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein by NMR Exchange Spectroscopy.
Linear Mode
