Low-affinity platelet factor 4 sup 1 H NMR derived aggregate equilibria indicate a physiologic preference for monomers over dimers and tetramers

Journal Article · Mon Jan 28 23:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00218a007· OSTI ID:5594809

Mayo, K H ^[1]

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1. Temple Univ., Philadelphia, PA (USA)

Low-affinity platelet factor 4 (LA-PF4), unlike another related, sequentially homologous platelet specific protein, platelet factor 4 (PF4), is an active mitogenic and chemotactic agent. PF4 exhibits a high binding affinity for heparin, while LA-PF4 does not. Both PF4 and LA-PF4 can exist in dimer and tetramer aggregate states. Equilibrium constants for PF4 aggregation have recently been estimated from fractional populations derived from proton nuclear magnetic resonance (NMR) integrals assigned to resonances in monomer, dimer, and tetramer states. On a 500-MHzNMR time scale, relatively slow exchange among LA-PF4 aggregate species has also allowed Tyr 15 ring proton resonances to be assigned for monomer, dimer, and tetramer states in LA-PF4. As a function of pH and ionic strength, equilibrium association constants for LA-PF4 dimer (K{sub D}) and tetramer (K{sub T}) formation have been estimated from Tyr 15 ring proton resonance integrals. Analysis of the pH dependence of K{sub D} and K{sub T} suggests that electrostatic interactions probably among Glu/Asp and Lys/Arg side chains form the predominant force in the monomer-monomer binding process, i.e., K{sub D}, while like-charge repulsion due to proximal, intersubunit Glu/Asp residues decreases K{sub T} as the pH is raised. At pH 7 and low ionic strength, the dimer state is highly favored over the tetramer state. Elevating the solvent ionic strength at pH 7 destabilizes the dimer state. Under these more physiologic conditions, i.e., pH 7 and 0.1-0.2 M NaCl, LA-PF4 monomers are highly favored over dimers and tetramers. For PF4 under similar solvent conditions, tetramers predominate. Differences in biological activities between these homologous platelet-specific proteins may be the result, at least in part, of differing aggregation properties.

• OSTI ID: 5594809
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:4; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
BARYONS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION FACTORS
BLOOD PLATELETS
BODY FLUIDS
COAGULANTS
DRUGS
ELEMENTARY PARTICLES
EQUILIBRIUM
FERMIONS
HADRONS
HEMATOLOGIC AGENTS
KINETICS
MAGNETIC RESONANCE
MATERIALS
NUCLEAR MAGNETIC RESONANCE
NUCLEONS
ORGANIC COMPOUNDS
OVERHAUSER EFFECT
PH VALUE
PHYSIOLOGY
PROTEINS
PROTONS
REACTION KINETICS
RESONANCE