title: Dynamics and thermodynamic properties of CXCL7 chemokine.
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 of CXCL7, 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 state dynamics. 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.
authors: Department of Physics and Optical Science, University of North Carolina, Charlotte, North Carolina, 28223.
authors: Charles A
authors: CA
authors: Herring
authors: Department of Physics and Optical Science, University of North Carolina, Charlotte, North Carolina, 28223.
authors: Christopher M
authors: CM
authors: Singer
authors: Kazan Institute of Biochemistry and Biophysics, Kazan, 40111, Russia.
authors: Elena A
authors: EA
authors: Ermakova
authors: Kazan Institute of Biochemistry and Biophysics, Kazan, 40111, Russia.
authors: Bulat I
authors: BI
authors: Khairutdinov
authors: Kazan Institute of Biochemistry and Biophysics, Kazan, 40111, Russia.
authors: Yuriy F
authors: YF
authors: Zuev
authors: Department of Physics and Optical Science, University of North Carolina, Charlotte, North Carolina, 28223.|Center for Biomedical Engineering, University of North Carolina, Charlotte, North Carolina, 28223.
authors: Donald J
authors: DJ
authors: Jacobs
authors: Department of Physics and Optical Science, University of North Carolina, Charlotte, North Carolina, 28223.|Center for Biomedical Engineering, University of North Carolina, Charlotte, North Carolina, 28223.
authors: Irina V
authors: IV
authors: Nesmelova
mesh_terms: D002942:Circular Dichroism; D004220:Disulfides; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D055503:Protein Multimerization; D055550:Protein Stability; D058767:Protein Unfolding; D013816:Thermodynamics; D001620:beta-Thromboglobulin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004220:Disulfides; C061615:PPBP protein, human; D001620:beta-Thromboglobulin
keywords: CD spectroscopy; CXCL7; chemokine; dimer; distance constraint model; disulfide bonds; dynamics; thermal unfolding