[NMR paper] The role of electrostatic interactions in binding of peptides and intrinsically disordered proteins to their folded targets. 1. NMR and MD characterization of the complex between c-Crk N SH3 domain and peptide Sos.
The role of electrostatic interactions in binding of peptides and intrinsically disordered proteins to their folded targets. 1. NMR and MD characterization of the complex between c-Crk N SH3 domain and peptide Sos.
Related ArticlesThe role of electrostatic interactions in binding of peptides and intrinsically disordered proteins to their folded targets. 1. NMR and MD characterization of the complex between c-Crk N SH3 domain and peptide Sos.
Biochemistry. 2014 Sep 10;
Authors: Xue Y, Yuwen T, Zhu F, Skrynnikov NR
Abstract
Intrinsically disordered proteins (IDPs) often rely on electrostatic interactions to bind their structured targets. To obtain insight into the mechanism of formation of electrostatic encounter complex, we investigated the binding of the peptide Sos (PPPVPPRRRR), which serves as a minimal model for an IDP, to the c Crk N-terminal SH3 domain. Initially, we measured 15N relaxation rates at two magnetic field strengths and determined the binding shifts for the complex of Sos with wild-type SH3. We have also recorded 3 ?s MD trajectory of this complex using Amber ff99SB*-ILDN force field. The comparison of the experimental and simulated data shows that MD simulation consistently overestimates the strength of salt-bridge interactions at the binding interface. The series of simulations using other advanced force fields also failed to produce any satisfactory results. To address this issue we have devised an empirical correction to Amber ff99SB*-ILDN force field whereby the Lennard-Jones equilibrium distance for nitrogen-oxygen pair across the Arg-to-Asp and Arg-to-Glu salt bridges has been increased by 3%. Implementing this correction resulted in a good agreement between the simulations and the experiment. Adjusting the strength of salt-bridge interactions removed a certain amount of strain contained in the original MD model, thus improving the binding of the hydrophobic N-terminal portion of the peptide. The arginine-rich C-terminal portion of the peptide, freed from the effect of the over-stabilized salt bridges, was found to interconvert more rapidly between its multiple conformational states. The modified MD protocol has been successfully used to simulate the entire binding process. In doing so, the peptide was initially placed high above the protein surface. It then arrived to the correct bound pose within ca. 2 Å of the crystallographic coordinates. This simulation allowed us to analyze the details of the dynamic binding intermediate, i.e. the electrostatic encounter complex. However, an experimental characterization of this transient, low-populated state remains out of reach. To overcome this problem, we designed the double mutant of c-Crk N-SH3 where the mutations Y186L/W169F abrogate tight Sos binding and shift the equilibrium toward the intermediate state resembling the electrostatic encounter complex. The results of the combined NMR and MD study of this engineered system will be reported in the next part of this paper.
PMID: 25207671 [PubMed - as supplied by publisher]
[NMR paper] Electrostatic interactions in the binding pathway of a transient protein complex studied by NMR and isothermal titration calorimetry.
Electrostatic interactions in the binding pathway of a transient protein complex studied by NMR and isothermal titration calorimetry.
Related Articles Electrostatic interactions in the binding pathway of a transient protein complex studied by NMR and isothermal titration calorimetry.
J Biol Chem. 2014 Aug 13;
Authors: Meneses E, Mittermaier A
Abstract
Much of our knowledge of protein binding pathways is derived from extremely stable complexes that interact very tightly, with lifetimes of hours to days. Much less is known about...
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[NMR paper] On the role of NMR spectroscopy for characterization of antimicrobial peptides.
On the role of NMR spectroscopy for characterization of antimicrobial peptides.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles On the role of NMR spectroscopy for characterization of antimicrobial peptides.
Methods Mol Biol. 2013;1063:159-80
Authors: Porcelli F, Ramamoorthy A, Barany G, Veglia G
Abstract
Antimicrobial peptides (AMPs) provide a primordial source of immunity, conferring upon eukaryotic cells resistance against bacteria,...
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[NMR paper] NMR based solvent exchange experiments to understand the conformational preference of intrinsically disordered proteins using FG-nucleoporin peptide as a model.
NMR based solvent exchange experiments to understand the conformational preference of intrinsically disordered proteins using FG-nucleoporin peptide as a model.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2250-98-WileyOnlineLibrary-Button_120x27px_FullText.gif Related Articles NMR based solvent exchange experiments to understand the conformational preference of intrinsically disordered proteins using FG-nucleoporin peptide as a model.
Biopolymers. 2013 Sep 4;
Authors: Heisel KA, Krishnan VV
...
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[NMR paper] Structural characterization of intrinsically disordered proteins by NMR spectroscopy.
Structural characterization of intrinsically disordered proteins by NMR spectroscopy.
Structural characterization of intrinsically disordered proteins by NMR spectroscopy.
Molecules. 2013;18(9):10802-28
Authors: Kosol S, Contreras-Martos S, Cedeño C, Tompa P
Abstract
Recent advances in NMR methodology and techniques allow the structural investigation of biomolecules of increasing size with atomic resolution. NMR spectroscopy is especially well-suited for the study of intrinsically disordered proteins (IDPs) and intrinsically disordered...
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[NMR paper] Role of hydrophobic interactions in the encounter complex formation of plastocyanin and cytochrome f complex revealed by paramagnetic NMR spectroscopy.
Role of hydrophobic interactions in the encounter complex formation of plastocyanin and cytochrome f complex revealed by paramagnetic NMR spectroscopy.
Role of hydrophobic interactions in the encounter complex formation of plastocyanin and cytochrome f complex revealed by paramagnetic NMR spectroscopy.
J Am Chem Soc. 2013 Apr 29;
Authors: Scanu S, Förster J, Ullmann GM, Ubbink M
Abstract
Protein complex formation is thought to be at least a two-step process, in which the active complex is preceded by the formation of an encounter complex....
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Intrinsically disordered proteins - PhysicsToday.org
Intrinsically disordered proteins - PhysicsToday.org
<img alt="" height="1" width="1" />
Intrinsically disordered proteins
PhysicsToday.org
Indeed, much of the community's understanding of protein function rests on our ability to deduce those structures by such methods as x-ray crystallography and nuclear magnetic resonance (NMR). The immense success and explanatory power of the ...
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08-01-2012 09:35 PM
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
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[NMR paper] Characterization of tertiary interactions in a folded protein by NMR methods: studies
Characterization of tertiary interactions in a folded protein by NMR methods: studies of pH-induced structural changes in human growth hormone.
Related Articles Characterization of tertiary interactions in a folded protein by NMR methods: studies of pH-induced structural changes in human growth hormone.
Biochemistry. 1992 Sep 15;31(36):8587-96
Authors: Abildgaard F, Jørgensen AM, Led JJ, Christensen T, Jensen EB, Junker F, Dalbøge H
The pH-induced conformational changes in human growth hormone (hGH) have been studied, using a new...