دورية أكاديمية
O-linked glycosylation of von Willebrand factor modulates the interaction with platelet receptor glycoprotein Ib under static and shear stress conditions.
| العنوان: | O-linked glycosylation of von Willebrand factor modulates the interaction with platelet receptor glycoprotein Ib under static and shear stress conditions. |
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| المؤلفون: | Nowak AA; Department of Haematology, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, London, UK., Canis K, Riddell A, Laffan MA, McKinnon TA |
| المصدر: | Blood [Blood] 2012 Jul 05; Vol. 120 (1), pp. 214-22. Date of Electronic Publication: 2012 Apr 19. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Blood Platelets/*physiology , Membrane Glycoproteins/*metabolism , Polysaccharides/*metabolism , von Willebrand Factor/*genetics , von Willebrand Factor/*metabolism, Anti-Bacterial Agents/pharmacology ; Binding Sites/physiology ; Collagen/metabolism ; Genetic Variation ; Glycosylation ; HEK293 Cells ; Humans ; Membrane Glycoproteins/chemistry ; Mutagenesis/physiology ; Platelet Glycoprotein GPIb-IX Complex ; Protein Binding/drug effects ; Protein Binding/physiology ; Protein Structure, Tertiary/physiology ; Recombinant Proteins/metabolism ; Regional Blood Flow/physiology ; Ristocetin/pharmacology ; Stress, Mechanical ; von Willebrand Factor/chemistry |
| مستخلص: | We have examined the effect of the O-linked glycan (OLG) structures of VWF on its interaction with the platelet receptor glycoprotein Ibα. The 10 OLGs were mutated individually and as clusters (Clus) on either and both sides of the A1 domain: Clus1 (N-terminal side), Clus2 (C-terminal side), and double cluster (DC), in both full-length-VWF and in a VWF construct spanning D' to A3 domains. Mutations did not alter VWF secretion by HEK293T cells, multimeric structure, or static collagen binding. The T1255A, Clus1, and DC variants caused increased ristocetin-mediated GPIbα binding to VWF. Platelet translocation rate on OLG mutants was increased because of reduced numbers of GPIbα binding sites but without effect on bond lifetime. In contrast, OLG mutants mediated increased platelet capture on collagen under high shear stress that was associated with increased adhesion of these variants to the collagen under flow. These findings suggest that removal of OLGs increases the flexibility of the hinge linker region between the D3 and A1 domain, facilitating VWF unfolding by shear stress, thereby enhancing its ability to bind collagen and capture platelets. These data demonstrate an important functional role of VWF OLGs under shear stress conditions. |
| معلومات مُعتمدة: | PG/11/50/28984 United Kingdom BHF_ British Heart Foundation; FS/06/064/21 490 United Kingdom BHF_ British Heart Foundation; RG/06/007 United Kingdom BHF_ British Heart Foundation |
| المشرفين على المادة: | 0 (Anti-Bacterial Agents) 0 (Membrane Glycoproteins) 0 (Platelet Glycoprotein GPIb-IX Complex) 0 (Polysaccharides) 0 (Recombinant Proteins) 0 (adhesion receptor) 0 (von Willebrand Factor) 1404-55-3 (Ristocetin) 9007-34-5 (Collagen) |
| تواريخ الأحداث: | Date Created: 20120421 Date Completed: 20120918 Latest Revision: 20220331 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1182/blood-2012-02-410050 |
| PMID: | 22517896 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood-2012-02-410050 |