Journal Articles

Dynamics and thermodynamic properties of CXCL7 chemokine

August 22, 2015

Dynamics and thermodynamic properties of CXCL7 chemokineProteins. 2015 Aug 22, Herring CA1, Singer CM1, Ermakova EA2, Khairutdinov BI2, Zuev YF2, Jacobs DJ1,3, Nesmelova IV1,3.

  • 1Department of Physics and Optical Science, University of North Carolina, Charlotte, NC, 28223, USA.
  • 2Kazan Institute of Biochemistry and Biophysics, Kazan, 40111, Russia.
  • 3Center for Biomedical Engineering, University of North Carolina, Charlotte, NC, 28223, USA.

The David H. Murdock Research Institute performed the NMR work for this paper.

Abstract

Chemokines form a family of signaling proteins mainly responsible for directing the traffic of leukocytes, where their biological activity can be modulated by their oligomerization state. We characterize the dynamics and thermodynamic stability of monomer and homodimer structures ofCXCL7, one of the most abundant platelet chemokines, using experimental methods that include Circular Dichroism (CD) and Nuclear Magnetic Resonance (NMR) spectroscopy, and computational methods that include the Anisotropic Network Model (ANM), Molecular Dynamics (MD) simulations and the Distance Constraint Model (DCM). A consistent picture emerges for the effects of dimerization and Cys5-Cys31 and Cys7-Cys47 disulfide bonds formation. The presence of disulfide bonds is not critical for maintaining structural stability in the monomer or dimer, but the monomer is destabilized more than the dimer upon removal of disulfide bonds. Disulfide bonds play a key role in shaping the characteristics of native statedynamics. The combined analysis shows that upon dimerization flexibly correlated motions are induced between the 30s and 50s loop within each monomer and across the dimer interface. Interestingly, the greatest gain in flexibility upon dimerization occurs when both disulfide bonds are present, and the homodimer is least stable relative to its two monomers. These results suggest that the highly conserved disulfide bonds in chemokines facilitate a structural mechanism that is tuned to optimally distinguish functional characteristics between monomer and dimer. This article is protected by copyright. All rights reserved.

© 2015 Wiley Periodicals, Inc.

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