Exploring platelet chemokine antimicrobial activity: NMR backbone dynamics studies of NAP-2 and TC-1.
Antimicrob Agents Chemother. 2011 Feb 14;
Authors: Nguyen LT, Kwakman PH, Chan DI, Liu Z, de Boer L, Zaat SA, Vogel HJ
The platelet chemokines NAP-2 and TC-1 differ by only two amino acids at their carboxy-terminal end. Nevertheless they display a significant difference in their direct antimicrobial activity, with the longer NAP-2 being inactive and TC-1 being active. In an attempt to rationalize this difference in activity we have studied the structure and the dynamics of both proteins by NMR spectroscopy. Using (15)N isotope-labeled protein, we confirmed that the two monomeric proteins essentially have the same overall structure in aqueous solution. However NMR relaxation measurements provided evidence that the negatively charged carboxy-terminal residues of NAP-2 experience a restricted motion, while the carboxy-terminal end of TC-1 moves in an unrestricted manner. The same behavior was also seen in molecular dynamics simulations of both proteins. Detailed analysis of the protein motions through model-free analysis, as well as a determination of their overall correlation times, provided evidence for the existence of a monomer-dimer equilibrium in solution, which seemed to be more prevalent for TC-1. This finding was supported by diffusion NMR experiments. Dimerization generates a larger cationic surface area that would increase the antimicrobial activity of these chemokines. Moreover these data also show that the negatively charged carboxy-terminal end of NAP-2 (which is absent in TC-1) folds back over part of the positively charged helical region of the protein and in doing so interferes with the direct antimicrobial activity.
PMID: 21321145 [PubMed - as supplied by publisher]
Recent Developments in (15)N NMR Relaxation Studies that Probe Protein Backbone Dynamics.
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Recent Developments in (15)N NMR Relaxation Studies that Probe Protein Backbone Dynamics.
Top Curr Chem. 2011 Sep 7;
Authors: Ishima R
Abstract
Nuclear Magnetic Resonance (NMR) relaxation is a powerful technique that provides information about internal dynamics associated with configurational energetics in proteins, as well as site-specific information involved in conformational equilibria. In particular, (15)N relaxation is a useful probe to...
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Chembiochem. 2010 Nov 22;11(17):2424-32
Authors: Díaz MD, Palomino-Schätzlein M, Corzana F, Andreu C, Carbajo RJ, del Olmo M, Canales-Mayordomo A, Pineda-Lucena A, Asensio G, Jiménez-Barbero J
The conformations of two synthetic pentapeptides with...
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05-04-2011 04:14 PM
NMR backbone dynamics studies of human PED/PEA-15 outline protein functional sites.
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NMR backbone dynamics studies of human PED/PEA-15 outline protein functional sites.
FEBS J. 2010 Sep 3;
Authors: Farina B, Pirone L, Russo L, Viparelli F, Doti N, Pedone C, Pedone EM, Fattorusso R
PED/PEA-15 (phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes) is a ubiquitously expressed protein and a key regulator of cell growth and glucose metabolism. PED/PEA-15 mediates both homotypic and heterotypic interactions and is constituted by...
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09-10-2010 11:53 PM
Backbone Amide Dynamics Studies of Apo-L75F-TrpR, a Temperature-Sensitive Mutant of t
Backbone Amide Dynamics Studies of Apo-L75F-TrpR, a Temperature-Sensitive Mutant of the Tryptophan Repressor Protein (TrpR): Comparison with the 15N NMR Relaxation Profiles of Wild-Type and A77V Mutant Apo-TrpR Repressors
http://pubs.acs.org//appl/literatum/publisher/achs/journals/content/bichaw/0/bichaw.ahead-of-print/bi100508u/aop/images/medium/bi-2010-00508u_0005.gifBiochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable).
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Authors: MacKay JP, Shaw GL, King GF
The backbone dynamics of the coiled-coil leucine zipper domain of c-Jun have been studied using proton-detected two-dimensional 1H-15N NMR spectroscopy. Longitudinal (T1) and transverse (T2) 15N relaxation times,...
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08-21-2010 11:16 PM
Backbone amide dynamics studies of apo-L75F-TrpR, a temperature sensitive mutant of t
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Biochemistry. 2010 Aug 18;
Authors: Goel A, Tripet BP, Tyler RC, Nebert LD, Copie V
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Exploring platelet chemokine antimicrobial activity: NMR backbone dynamics studies of NAP-2 and TC-1.
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