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

Petruk, Ganna LU orcid ; Petrlova, Jitka LU ; Samsudin, Firdaus ; Bond, Peter J. and Schmidtchen, Artur LU (2024) In Heliyon 10(16).
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... (More)

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, in silico 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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Heliyon
volume
10
issue
16
article number
e35703
publisher
Elsevier
external identifiers
  • pmid:39229523
  • scopus:85201007606
ISSN
2405-8440
DOI
10.1016/j.heliyon.2024.e35703
language
English
LU publication?
yes
id
2fb22fe4-6819-43c7-a6b3-f5f9336f489e
date added to LUP
2024-09-06 14:10:26
date last changed
2024-09-07 03:00:04
@article{2fb22fe4-6819-43c7-a6b3-f5f9336f489e,
  abstract     = {{<p>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, in silico 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.</p>}},
  author       = {{Petruk, Ganna and Petrlova, Jitka and Samsudin, Firdaus and Bond, Peter J. and Schmidtchen, Artur}},
  issn         = {{2405-8440}},
  language     = {{eng}},
  number       = {{16}},
  publisher    = {{Elsevier}},
  series       = {{Heliyon}},
  title        = {{Thrombin-derived C-terminal peptides bind and form aggregates with sulfated glycosaminoglycans}},
  url          = {{http://dx.doi.org/10.1016/j.heliyon.2024.e35703}},
  doi          = {{10.1016/j.heliyon.2024.e35703}},
  volume       = {{10}},
  year         = {{2024}},
}