Inhibition of Protein Aggregation: SAXS Study on the Role of the αC Region of Fibrinogen in the Fibrin Polymerization

Abstract:

Fibrin polymerization proceeds in a stepwise manner. In the first step, fibrinogen-to-fibrin conversion is triggered by the enzymatic fibrinopeptide release and protofibril formation/growth proceeds. In the following second step, lateral aggregation of the protofibrils occurs resulting in the network formation. Switchover from the first step to the second one can regulate the resultant network structure, and the lateral aggregation is considered to be induced by the interaction between the αC regions of two adjacent protofibrils. In order to clarify the characteristics of this interaction, we examined the cross-sectional diameter D_C in addition to the hydrodynamic diameter (Stoke diameter) of fibrinogen molecule in various solution conditions. Cross-sectional diameter of intact fibrinogen was 4.7 nm in agreement with the molecular structure. On the other hand, fragment-X, in which the αC regions are deleted, had smaller D_C of 4.2 nm. This means that the αC regions snuggle up to the molecular backbone, which is consistent with the model that the termini of the αC regions are tethered to the central E-region in the intact fibrinogen. On the other hand, fibrinogen at pH 3 had a cross-sectional diameter of 4.0 nm, which is further smaller than that of fragment-X. This is accounted for by the scheme that the αC regions are released from the central region, because side chains of Asp and Glu residues have neutral charge at pH 3. With the increase of ionic strength up to 150 mM at pH 3, fibrinogen molecules become to aggregate resulting in huge aggregated particles. Our results suggest that the released αC regions can interact attractively with each other through the hydrophobic interaction, which supports the proposed scheme of fibrin polymerization.

• Periodical: Key Engineering Materials (Volume 497)
• Pages: 41-46
• DOI: https://doi.org/10.4028/www.scientific.net/KEM.497.41
• Online since: December 2011
• Authors: Kenji Kubota, Kaori Wakamatsu, Nobukazu Nameki, Yoshiharu Toyama
• Keywords: Fibrin Polymerization, Fibrinogen, Fragment-X, Light Scattering, SAXS, αC Region

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