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Human platelet factor 4 subunit association/dissociation thermodynamics and kinetics

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00240a009· OSTI ID:5013983
;  [1]
  1. Temple Univ., Philadelphia, PA (United States)

Platelet factor 4 (PF4) monomers (7,800 daltons) form dimers and tetramers in varying molar ratios under certain solution conditions. The presence of a simplified aromatic region (one Try and two His) and resolved monomer, dimer, and tetramer Y60 3,5 ring proton resonances makes study of PF4 aggregate association/dissociation thermodynamics and kinetics possible. PF4 protein subunit association/dissociation equilibrium thermodynamic parameters have been derived by {sup 1}H NMR (500 MHz) resonance line-fitting analysis of steady-state Y60 3,5 ring proton resonance monomer-dimer-tetramer populations as a function of temperature from 10 to 40 C. The thermodynamic parameters are consistent with low dielectric medium electrostatic/hydrophobic interactions governing dimer formation and hydrogen bonding governing tetramer formation. Association/dissociation kinetic parameters, i.e., steady-state jump rates, have been derived form exchange-induced linme-width increases and from {sup 1}H NMR (500 MHz) saturation-transfer and spin-lattice (T{sub 1}) relaxation experiments. From dissociation jump rates and equilibrium constants, association rate constants were estimated. Kinetically, tetramers are preferred over dimers due primarily to a slower dissociation rate, and thermo-dynamically, tetramer formation is enthalpy-driven, while dimerization is entropy-driven.

OSTI ID:
5013983
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:26; ISSN 0006-2960; ISSN BICHA
Country of Publication:
United States
Language:
English