Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14
| العنوان: | Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14 |
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| المؤلفون: | Richard J. Payne, Meritxell Canals, Martin J. Stone, Mark Larance, Julie Sanchez, Leo Corcilius, Siyao Wang, Simon R. Foster |
| المصدر: | ACS Chemical Biology. 16:973-981 |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, CCR1, Leukocyte migration, Chemokine, Glycosylation, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Chemokine receptor, Protein Domains, Humans, Amino Acid Sequence, CCL14, biology, 010405 organic chemistry, Chemistry, General Medicine, Ligand (biochemistry), Native chemical ligation, 0104 chemical sciences, Cell biology, 030104 developmental biology, Chemokines, CC, Proteolysis, biology.protein, Molecular Medicine |
| الوصف: | Chemokines are secreted proteins that regulate leukocyte migration during inflammatory responses by signaling through chemokine receptors. Full length CC chemokine ligand 14, CCL14(1-74), is a weak agonist for the chemokine receptor CCR1, but its activity is substantially enhanced upon proteolytic cleavage to CCL14(9-74). CCL14 is O-glycosylated at Ser7, adjacent to the site of proteolytic activation. To determine whether glycosylation regulates the activity of CCL14, we used native chemical ligation to prepare four homogeneously glycosylated variants of CCL14(1-74). Each protein was assembled from three synthetic peptide fragments in "one-pot" using two sequential ligation reactions. We show that while glycosylation of CCL14(1-74) did not affect CCR1 binding affinity or potency of activation, sialylated variants of CCL14(1-74) exhibited reduced activity after treatment with plasmin compared to nonsialylated forms. These data indicate that glycosylation may influence the biological activity of CCL14 by regulating its conversion from the full-length to the truncated, activated form. |
| تدمد: | 1554-8937 1554-8929 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39029be6bfe67b55fdf5711513491483Test https://doi.org/10.1021/acschembio.1c00006Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....39029be6bfe67b55fdf5711513491483 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548937 15548929 |
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