The Biological Significance of von Willebrand Factor O-Linked Glycosylation

Soracha Ward; Jamie M. O'Sullivan; James S. O'Donnell

doi:10.1055/s-0041-1726373

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2021; 47(07): 855-861
DOI: 10.1055/s-0041-1726373

Review Article

The Biological Significance of von Willebrand Factor O-Linked Glycosylation

Soracha Ward

¹Haemostasis Research Group, Irish Centre for Vascular Biology, School of Pharmacy and Bimolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland

,

Jamie M. O'Sullivan

¹Haemostasis Research Group, Irish Centre for Vascular Biology, School of Pharmacy and Bimolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland

,

James S. O'Donnell

¹Haemostasis Research Group, Irish Centre for Vascular Biology, School of Pharmacy and Bimolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland

²National Coagulation Centre, St James's Hospital, Dublin, Ireland

› Institutsangaben

Abstract

Glycosylation is a key posttranslational modification, known to occur on more than half of all secreted proteins in man. As such, the role of N- and O-linked glycan structures in modulating various aspects of protein biology is an area of much research. Given their prevalence, it is perhaps unsurprising that variations in glycan structures have been demonstrated to play critical roles in modulating protein function and have been implicated in the pathophysiology of human diseases. von Willebrand factor (VWF), a plasma glycoprotein that is essential for normal hemostasis, is heavily glycosylated, containing 13 N-linked and 10 O-linked glycans. Together, these carbohydrate chains account for 20% of VWF monomeric mass, and have been shown to modulate VWF structure, function, and half-life. In this review, we focus on the specific role played by O-linked glycans in modulating VWF biology. Specifically, VWF O-linked glycans have been shown to modulate tertiary protein structure, susceptibility to ADAMTS13 proteolysis, platelet tethering, and VWF circulatory half-life.

Keywords

von Willebrand factor - O glycan - lectin - glycan - clearance

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Referenzen

References
1 Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 1998; 67 (01) 395-424
2 Nichols WL, Rick ME, Ortel TL. et al. Clinical and laboratory diagnosis of von Willebrand disease: a synopsis of the 2008 NHLBI/NIH guidelines. Am J Hematol 2009; 84 (06) 366-370
3 Samor B, Mazurier C, Goudemand M, Debeire P, Fournet B, Montreuil J. Preliminary results on the carbohydrate moiety of factor VIII/von Willebrand factor (FVIII/vWf). Thromb Res 1982; 25 (1–2): 81-89
4 Ward S, O'Sullivan JM, O'Donnell JS. von Willebrand factor sialylation—A critical regulator of biological function. J Thromb Haemost 17 (07) 1018-1029
5 Kaufman RJ. Post-translational modifications required for coagulation factor secretion and function. Thromb Haemost 1998; 79 (06) 1068-1079
6 Lenting PJ, Christophe OD, Denis CV. von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends. Blood 2015; 125 (13) 2019-2028
7 Wagner DD, Marder VJ. Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization. J Cell Biol 1984; 99 (06) 2123-2130
8 Matsui T, Titani K, Mizuochi T. Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. Occurrence of blood group A, B, and H(O) structures. J Biol Chem 1992; 267 (13) 8723-8731
9 Titani K, Kumar S, Takio K. et al. Amino acid sequence of human von Willebrand factor. Biochemistry 1986; 25 (11) 3171-3184
10 Debeire P, Montreuil J, Samor B. et al. Structure determination of the major asparagine-linked sugar chain of human factor VIII--von Willebrand factor. FEBS Lett 1983; 151 (01) 22-26
11 Canis K, McKinnon TAJ, Nowak A. et al. Mapping the N-glycome of human von Willebrand factor. Biochem J 2012; 447 (02) 217-228
12 Canis K, McKinnon TAJ, Nowak A. et al. The plasma von Willebrand factor O-glycome comprises a surprising variety of structures including ABH antigens and disialosyl motifs. J Thromb Haemost 2010; 8 (01) 137-145
13 Samor B, Michalski JC, Mazurier C. et al. Primary structure of the major O-glycosidically linked carbohydrate unit of human von Willebrand factor. Glycoconj J 1989; 6 (03) 263-270
14 Solecka BA, Weise C, Laffan MA, Kannicht C. Site-specific analysis of von Willebrand factor O-glycosylation. J Thromb Haemost 2016; 14 (04) 733-746
15 Varki A, Cummings RD, Esko JD. et al, eds. Essentials of Glycobiology, 3rd ed. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2015
16 Bennett EP, Mandel U, Clausen H, Gerken TA, Fritz TA, Tabak LA. Control of mucin-type O-glycosylation: a classification of the polypeptide GalNAc-transferase gene family. Glycobiology 2012; 22 (06) 736-756
17 Hanisch FG. O-glycosylation of the mucin type. Biol Chem 2001; 382 (02) 143-149
18 Uhlenbruck G. The Thomsen-Friedenreich (TF) receptor: an old history with new mystery. Immunol Commun 1981; 10 (03) 251-264
19 McGrath RT, McKinnon TAJ, Byrne B. et al. Expression of terminal alpha2-6-linked sialic acid on von Willebrand factor specifically enhances proteolysis by ADAMTS13. Blood 2010; 115 (13) 2666-2673
20 Storr SJ, Royle L, Chapman CJ. et al. The O-linked glycosylation of secretory/shed MUC1 from an advanced breast cancer patient's serum. Glycobiology 2008; 18 (06) 456-462
21 Gashash EA, Aloor A, Li D. et al. An insight into glyco-microheterogeneity of plasma von Willebrand factor by mass spectrometry. J Proteome Res 2017; 16 (09) 3348-3362
22 Ward S, O'Sullivan J, O'Donnell JS. The relationship between ABO blood group, von Willebrand factor and primary hemostasis. Blood 2020; 2020005843
23 McGrath RT, McRae E, Smith OP, O'Donnell JS. Platelet von Willebrand factor--structure, function and biological importance. Br J Haematol 2010; 148 (06) 834-843
24 McGrath RT, van den Biggelaar M, Byrne B. et al. Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis. Blood 2013; 122 (25) 4107-4110
25 McKinnon TAJ, Goode EC, Birdsey GM. et al. Specific N-linked glycosylation sites modulate synthesis and secretion of von Willebrand factor. Blood 2010; 116 (04) 640-648
26 Carew JA, Quinn SM, Stoddart JH, Lynch DC. O-linked carbohydrate of recombinant von Willebrand factor influences ristocetin-induced binding to platelet glycoprotein 1b. J Clin Invest 1992; 90 (06) 2258-2267
27 Nowak AA, Canis K, Riddell A, Laffan MA, McKinnon TAJ. O-linked glycosylation of von Willebrand factor modulates the interaction with platelet receptor glycoprotein Ib under static and shear stress conditions. Blood 2012; 120 (01) 214-222
28 Badirou I, Kurdi M, Legendre P. et al. In vivo analysis of the role of O-Glycosylations of von Willebrand factor. PLoS One 2012; 7 (05) e37508
29 Jentoft N. Why are proteins O-glycosylated?. Trends Biochem Sci 1990; 15 (08) 291-294
30 Tischer A, Machha VR, Moon-Tasson L, Benson LM, Auton M. Glycosylation sterically inhibits platelet adhesion to von Willebrand factor without altering intrinsic conformational dynamics. J Thromb Haemost 2020; 18 (01) 79-90
31 Deng W, Wang Y, Druzak SA. et al. A discontinuous autoinhibitory module masks the A1 domain of von Willebrand factor. J Thromb Haemost 2017; 15 (09) 1867-1877
32 Nowak AA, McKinnon TAJ, Hughes JM, Chion ACK, Laffan MA. The O-linked glycans of human von Willebrand factor modulate its interaction with ADAMTS-13. J Thromb Haemost 2014; 12 (01) 54-61
33 Furlan M, Robles R, Lämmle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood 1996; 87 (10) 4223-4234
34 Tsai HM. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion. Blood 1996; 87 (10) 4235-4244
35 Goettig P. Effects of glycosylation on the enzymatic activity and mechanisms of proteases. Int J Mol Sci 2016; 17 (12) E1969
36 Preston RJS, Rawley O, Gleeson EM, O'Donnell JS. Elucidating the role of carbohydrate determinants in regulating hemostasis: insights and opportunities. Blood 2013; 121 (19) 3801-3810
37 O'Donnell JS, McKinnon TAJ, Crawley JTB, Lane DA, Laffan MA. Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis. Blood 2005; 106 (06) 1988-1991
38 McKinnon TAJ, Chion ACK, Millington AJ, Lane DA, Laffan MA. N-linked glycosylation of VWF modulates its interaction with ADAMTS13. Blood 2008; 111 (06) 3042-3049
39 Schulte am Esch II J, Robson SC, Knoefel WT, Eisenberger CF, Peiper M, Rogiers X. Impact of O-linked glycosylation of the VWF-A1-domain flanking regions on platelet interaction. Br J Haematol 2005; 128 (01) 82-90
40 Ulrichts H, Udvardy M, Lenting PJ. et al. Shielding of the A1 domain by the D'D3 domains of von Willebrand factor modulates its interaction with platelet glycoprotein Ib-IX-V. J Biol Chem 2006; 281 (08) 4699-4707
41 Tischer A, Cruz MA, Auton M. The linker between the D3 and A1 domains of vWF suppresses A1-GPIbα catch bonds by site-specific binding to the A1 domain. Protein Sci 2013; 22 (08) 1049-1059
42 Johnsen JM, Auer PL, Morrison AC. et al; NHLBI Exome Sequencing Project. Common and rare von Willebrand factor (VWF) coding variants, VWF levels, and factor VIII levels in African Americans: the NHLBI Exome Sequencing Project. Blood 2013; 122 (04) 590-597
43 Chion A, O'Sullivan JM, Drakeford C. et al. N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. Blood 2016; 128 (15) 1959-1968
44 O'Sullivan JM, Aguila S, McRae E. et al. N-linked glycan truncation causes enhanced clearance of plasma-derived von Willebrand factor. J Thromb Haemost 2016; 14 (12) 2446-2457
45 O'Sullivan JM, Ward S, Lavin M, O'Donnell JS. von Willebrand factor clearance - biological mechanisms and clinical significance. Br J Haematol 2018; 183 (02) 185-195
46 Stoddart Jr JH, Andersen J, Lynch DC. Clearance of normal and type 2A von Willebrand factor in the rat. Blood 1996; 88 (05) 1692-1699
47 Sodetz JM, Pizzo SV, McKee PA. Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. J Biol Chem 1977; 252 (15) 5538-5546
48 Ellies LG, Ditto D, Levy GG. et al. Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands. Proc Natl Acad Sci U S A 2002; 99 (15) 10042-10047
49 Millar CM, Riddell AF, Brown SA. et al. Survival of von Willebrand factor released following DDAVP in a type 1 von Willebrand disease cohort: influence of glycosylation, proteolysis and gene mutations. Thromb Haemost 2008; 99 (05) 916-924
50 Aguila S, Lavin M, Dalton N. et al. Increased galactose expression and enhanced clearance in patients with low von Willebrand factor. Blood 2019; 133 (14) 1585-1596
51 van Schooten CJM, Denis CV, Lisman T. et al. Variations in glycosylation of von Willebrand factor with O-linked sialylated T antigen are associated with its plasma levels. Blood 2007; 109 (06) 2430-2437
52 O'Donnell JS. Low VWF: insights into pathogenesis, diagnosis, and clinical management. Blood Adv 2020; 4 (13) 3191-3199
53 Grewal PK, Uchiyama S, Ditto D. et al. The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med 2008; 14 (06) 648-655
54 Ward SE, O'Sullivan JM, Drakeford C. et al. A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. Blood 2018; 131 (08) 911-916