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凝血酶衍生的C末端肽与硫酸化糖胺聚糖结合并形成聚集体。

Thrombin-derived C-terminal peptides bind and form aggregates with sulfated glycosaminoglycans.

作者信息

Petruk Ganna, Petrlova Jitka, Samsudin Firdaus, Bond Peter J, Schmidtchen Artur

机构信息

Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 22241, Lund, Sweden.

Department of Biomedical Science, Faculty of Health and Society, Malmö University, SE-205 06, Malmö, Sweden.

出版信息

Heliyon. 2024 Aug 2;10(16):e35703. doi: 10.1016/j.heliyon.2024.e35703. eCollection 2024 Aug 30.

DOI:10.1016/j.heliyon.2024.e35703
PMID:39229523
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11369470/
Abstract

Glycosaminoglycans (GAGs) such as heparin and heparan sulfate (HS) play crucial roles in inflammation and wound healing, serving as regulators of growth factors and pro-inflammatory mediators. In this study, we investigated the influence of heparin/HS on thrombin proteolysis and its interaction with the generated 11 kDa thrombin-derived C-terminal peptides (TCPs). Employing various biochemical and biophysical methods, we demonstrated that 11 kDa TCPs aggregate in the presence of GAGs, including heparin, heparan sulfate, and chondroitin sulfate-B. Circular dichroism analysis demonstrated that 11 kDa TCPs, in the presence of GAGs, adopt a β-sheet structure, a finding supported by thioflavin T1 (ThT) fluorescence measurements and visualization of 11 kDa TCP-heparin complexes using transmission electron microscopy (TEM). Furthermore, our investigations revealed a stronger binding affinity between 11 kDa TCPs and GAGs with higher sulfate group contents. Congruently, simulations showed that interactions between 11 kDa TCPs and heparin/HS are predominantly electrostatic in nature. Collectively, our study suggests that 11 kDa TCPs have the capacity to aggregate in the presence of GAGs, shedding light on their potential roles in inflammation and wound healing.

摘要

糖胺聚糖（GAGs），如肝素和硫酸乙酰肝素（HS），在炎症和伤口愈合中发挥着关键作用，作为生长因子和促炎介质的调节剂。在本研究中，我们研究了肝素/HS对凝血酶蛋白水解的影响及其与生成的11 kDa凝血酶衍生C末端肽（TCPs）的相互作用。采用各种生化和生物物理方法，我们证明了11 kDa TCPs在GAGs（包括肝素、硫酸乙酰肝素和硫酸软骨素-B）存在下会聚集。圆二色性分析表明，在GAGs存在下，11 kDa TCPs呈现β-折叠结构，这一发现得到了硫黄素T1（ThT）荧光测量以及使用透射电子显微镜（TEM）对11 kDa TCP-肝素复合物进行可视化的支持。此外，我们的研究表明，11 kDa TCPs与硫酸基团含量较高的GAGs之间具有更强的结合亲和力。同样，模拟结果表明，11 kDa TCPs与肝素/HS之间的相互作用主要是静电性质的。总的来说，我们的研究表明，11 kDa TCPs在GAGs存在下具有聚集能力，这为它们在炎症和伤口愈合中的潜在作用提供了线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/ec87d9fa4ea7/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/07119412c29d/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/01338c2a2f3b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/f27bd91af0e6/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/ace62a3d0b30/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/06a1f018da28/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/26e7a6641b51/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/c41cebd4d77d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/ec87d9fa4ea7/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/07119412c29d/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/01338c2a2f3b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/f27bd91af0e6/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/ace62a3d0b30/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/06a1f018da28/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/26e7a6641b51/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/c41cebd4d77d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5e/11369470/ec87d9fa4ea7/gr7.jpg

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Thrombin: A Pivotal Player in Hemostasis and Beyond.凝血酶：止血与超越的关键角色。
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