Alternative Role of B/b Knob-Hole Interactions in the Fibrin Assembly.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry Biochemistry Pub Date : 2025-02-18 Epub Date: 2025-01-27 DOI:10.1021/acs.biochem.4c00695
Tatyana Platonova, Oleksii Hrabovskyi, Volodymyr Chernyshenko, Yevhenii Stohnii, Yevhenii Kucheriavyi, Kateryna Baidakova, Daria Korolova, Anna Urbanowicz, Serhiy Komisarenko
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Abstract

The self-assembly of fibrin is a vital process in blood clotting, primarily facilitated by the interactions between knobs "A" and "B" in the central E region of one molecule and the corresponding holes "a" and "b" in the peripheral D regions of two other fibrin molecules. However, the precise function of the interactions between knob "B" and hole "b" during fibrin polymerization remains a subject of ongoing debate. The present study focuses on investigating intermolecular interactions between knob "B" and hole "b". We investigated the D-E-D interactions within the fibrin protofibril to accomplish this objective. Our investigation involved studying the formation of supramolecular complexes involving desAB fibrin with fibrin(ogen) fragments, specifically the D-dimer and D fragment. The research utilized analytical size-exclusion chromatography, SDS-PAGE and densitometry of SDS-PAGE images, dynamic light scattering measurements, turbidity studies, electron microscopy, and computer modeling. Our findings indicate that the interference of the D fragment into classical D-E-D interaction occurs through knob "B" of the fibrin molecule. Molecular dynamics simulations elucidate the binding of only one D region, attributed to the shift of the D-dimer toward the fibrin desAB molecule. The formation of such a complex can be considered evidence supporting the potential mechanism of the branching of protofibrils. According to this theoretical mechanism, the inclusion of the D region from an external fibrin molecule into D-E-D interactions is facilitated through "B/b" contacts.

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Biochemistry Biochemistry
Biochemistry Biochemistry 生物-生化与分子生物学
CiteScore
5.50
自引率
3.40%
发文量
336
审稿时长
1-2 weeks
期刊介绍: Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.
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