Conformational Flexibility and Self-Association of Fibrinogen in Concentrated Solutions

• DOI: 10.1021/acs.jpcb.7b05654
• Publication Date: 2017-07-25T22:41:59Z
• Authors: Yuriy F. Zuev; Rustem I. Litvinov; Alexander E. Sitn...; Bulat Z. Idiyatullin; Dilyafruz R. Baki...; Dennis K. Galanakis; Artem Zhmurov; Valeri Barsegov; John W. Weisel
• Keywords: Models, Molecular; Solutions; 0303 health sciences; 03 medical and health sciences; Protein Conformation; Hydrodynamics; Fibrinogen; Humans; 540; Pliability; 530

We studied the hydrodynamic behavior of fibrinogen, a blood plasma protein involved in clotting, broad 0.3-60 mg/mL range concentration and 5-42 °C temperature using pulsed-field gradient 1H NMR-diffusometry. Arrhenius plots revealed activation energy for fibrinogen diffusion Ed = 21.3 kJ/mol at 1.4 28.4 38 mg/mL. found dramatic slowdown self-diffusion with beginning 1.7-3.4 mg/mL, which deviated from standard hard-particle behavior, suggesting remarkable intermolecular entanglement. This dependence was observed regardless absence or presence GPRP peptide (inhibitor fibrin polymerization), also samples free oligomers. By contrast, diffusivity variant I-9 truncated C-terminal portions Aα chains much less concentration-dependent, indicating importance linkages formed by αC regions. Theoretical models combined all-atom molecular dynamics simulations partially bent solution conformations that interpolate between flexible chain rigid rod crystal. The results obtained illuminate important role regions modulating shape through formation weak control bulk properties solutions.