Ristocetin-dependent, but not botrocetin-dependent, binding of von Willebrand factor to the platelet glycoprotein Ib-IX-V complex correlates with shear-dependent interactions

Dong, Jing‐fei; Berndt, Michael C.; Schade, Alicia J.; McIntire, Larry V.; Andrews, Robert K.; López, José A.

doi:10.1182/blood.v97.1.162

Cited by 132 publications

(141 citation statements)

References 38 publications

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“…First, they demonstrate that tyrosine sulfation influences the interaction between GP Ib␣ and vWF either by an electrostatic mechanism or by metal ion coordination, both of which can be replaced by the carboxylic acid-containing side chain of glutamic acid. Second, the correspondence between the effects of the mutations on shear-dependent vWF binding function and on ristocetin-induced vWF binding is consistent with our previous findings that ristocetin is a better mimic of the physiologic interaction than is botrocetin (41). The specific sequence is not as critical for ristocetin-induced binding as for botrocetin-induced binding, which is markedly perturbed by both the Phe and the Glu substitutions.…”

Section: Discussionsupporting

confidence: 77%

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Tyrosine Sulfation of Glycoprotein Ibα

Dong

Schade

et al. 2001

Journal of Biological Chemistry

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Glycoprotein Ib␣ (GP Ib␣), the ligand binding subunit of the platelet glycoprotein Ib-IX-V complex, is sulfated on three tyrosine residues (Tyr-276, Tyr-278, and Tyr-279). This posttranslational modification is known to be critical for von Willebrand factor (vWF) binding; yet it remains unclear whether it provides a specific structure or merely contributes negative charges. To investigate this issue, we constructed cell lines expressing GP Ib␣ polypeptides with the three tyrosine residues converted to either Glu or Phe and studied the ability of these mutants to bind vWF in the presence of modulators or shear stress. The mutants were expressed normally on the cell surface as GP Ib-IX complexes, with the conformation of the ligand-binding domain preserved, as judged by the binding of conformation-sensitive monoclonal antibodies. In contrast to their normal expression, both mutants were functionally abnormal. Cells expressing the Phe mutant failed to bind vWF in the presence of either ristocetin or botrocetin. These cells adhered to and rolled on immobilized vWF only when their surface receptor density was increased to twice the level that supported adhesion of cells expressing the wild-type receptor and even then only 20% as many rolled and rolled significantly faster than wild-type cells. Cells expressing the Glu mutant, on the other hand, were normal with respect to ristocetin-induced vWF binding and adhesion to immobilized vWF but were markedly defective in botrocetin-induced vWF binding. These results indicate that GP Ib␣ tyrosine sulfation influences the interaction of this polypeptide with vWF primarily by contributing negative charges under physiological conditions and when the interaction is induced by ristocetin but contributes a specific structure to the botrocetin-induced interaction.The platelet receptor for von Willebrand factor (vWF), 1 the glycoprotein (GP) Ib-IX-V complex, is composed of four polypeptide subunits (GP Ib␣, GP Ib␤, GP IX, and GP V (1, 2)) encoded by four separate genes (3-6). GP Ib␣ is the largest subunit within the complex and so far the only subunit implicated in ligand binding, being capable of binding vWF (7), ␣-thrombin (7), P-selectin (8), and leukocyte Mac-1 (9). The ligand-binding region resides within ϳ300 amino acids at the GP Ib␣ N terminus and is held high above the cell membrane by a stiff, highly O-glycosylated mucin-like domain ( Fig. 1) (3, 10). The ligandbinding region can be divided into three distinct structural subdomains that are all implicated in vWF binding (7): seven tandem leucine-rich repeats, disulfide loops flanking the leucine-rich repeats, and a highly negatively charged sequence spanning residues Asp-269 to Asp-287 (3, 10). Three tyrosine residues (Tyr-276, Tyr-278, and Tyr-279) are embedded in this negatively charged sequence (2, 7) and each is fully sulfated, a modification critical for the binding of vWF and ␣-thrombin (11-13).Tyrosine sulfation is a widespread posttranslational modification of proteins (14 -20), but few studies have addressed its e...

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Section: Discussionsupporting

confidence: 77%

“…4 upper), a modulator that we have recently demonstrated to more closely mimic physiological vWF binding, i.e. binding induced by high shear stress or by vWF immobilization onto a surface (41). This defect in ristocetin-induced vWF binding was indeed mimicked by a defect in attachment of the cells to immobilized vWF in a flow chamber.…”

Section: Discussionmentioning

confidence: 93%

Tyrosine Sulfation of Glycoprotein Ibα

Dong

Schade

et al. 2001

Journal of Biological Chemistry

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“…The differential inhibition of static and rolling adhesion may be related to the higher shear forces under flow conditions (rolling). As has been reported for recognition of vascular cell adhesion molecule (VCAM) 51 and von Willebrand factor (VWF), 52,53 shear can markedly modulate receptor-ligand interaction due to ligand tethering, protein folding, or site accessibility, which leads to a partial inhibition by the peptides. Interestingly, differential inhibition of P-selectin-mediated cell adhesion under static and rolling conditions was also observed for rPSGL-Ig, which gave full inhibition in static assays, but only enhancement of the rolling velocity under flow (Dr R. Schaub, personal oral communication, November 2001).…”

Section: Discussionmentioning

confidence: 99%

Specific inhibition of P-selectin–mediated cell adhesion by phage display–derived peptide antagonists

Molenaar

Appeldoorn

Haas

et al. 2002

Blood

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P-selectin is a leukocyte adhesion receptor expressed on activated vascular endothelium and platelets that mediates leukocyte rolling and attachment. Because P-selectin is critically involved in inflammation, we used phage display libraries to identify Pselectin-specific peptides that might interfere with its proinflammatory function. Isolated phage contained a highly conserved amino acid motif. Synthetic peptides showed calcium-dependent binding to P-selectin, with high selectivity over E-selectin and L-selectin. The peptides completely antagonized adhesion of monocyte-derived HL60 cells to P-selectin and increased their rolling velocities in flow chamber experiments. Peptide truncation and alanine-scanning studies indicated that an EWVDV (single-letter amino acid codes) consensus motif sufficed for effective inhibition. Intriguingly, the apparent avidity of the peptides was increased 200-fold when presented in a tetrameric form (2 M versus 10 nM), which is consistent with the proposed divalent interaction of P-selectin glycoprotein ligand 1 (PSGL-1) with P-selectin. As the EWVDV peptides inhibit the binding of an established glycoside ligand for P-selectin (sulfated Lewis A), it is conceivable that EWVDV interacts with or in close proximity to the actual carbohydrate recognition domain of P-selectin, without being a direct structural mimic of sialyl Lewis x . These ligands are among the most potent antagonists of Pselectin yet designed. Their high affinity, selectivity, and accessible synthesis provide a promising entry to the development of new anti-inflammatory therapeutics and might be a powerful tool to provide important information on the binding site of Pselectin. (Blood. 2002;100:3570-3577)

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“…Although SZ2 can block certain GPIb-related platelet functions, it is known to have no effect on shear-dependent VWFGPIb interactions (15). On the other hand, the function blocking antibody used in our study, LJIb1, does inhibit VWF binding to platelets under high shear stress (16).…”

Section: Discussionmentioning

confidence: 64%

Convulxin Binds to Native, Human Glycoprotein Ibα

Kanaji¹,

Kanaji²,

Furihata³

et al. 2003

Journal of Biological Chemistry

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Convulxin (CVX), a C-type snake protein from Crotalus durissus terrificus venom, is the quintessential agonist for studies of the collagen receptor, glycoprotein VI (GPVI) and its role in platelet adhesion to collagens. In this study, CVX, purified from venom, behaves as expected, i.e. it binds to platelet GPVI and recombinant human GPVI, induces platelet aggregation and platelet prothrombinase activity, and binds uniquely to GPVI in ligand blots of SDS-denatured proteins. Nonetheless, we find that CVX has a dual specificity for both GPVI and native but not denatured human GPIb␣. First, CVX binds to human GPIb␣ expressed on the surface of CHO cells. Second, CVX binds weakly to murine platelet GPIb␣ but more strongly to human platelet GPIb␣, as evidenced by comparative binding to wild-type, GPVI(؊/؊), FcR␥ (؊/؊), and human GPIb transgenic mice. Third, the binding of CVX to human GPIb␣ is inhibited by soluble, recombinant human GPVI. Fourth, CVX binding to GPIb␣ is disrupted by phenylalanine substitutions at GPIb␣ tyrosine-276, tyrosine-278, and tyrosine-279, which also disrupts von Willebrand factor and ␣-thrombin binding to GPIb␣. Fifth, CVX binding to GPIb␣ on Chinese hamster ovary cell transfectants is inhibited by function-blocking murine monoclonal anti-GPIb␣ antibodies. Lastly, CVX fails to bind to denatured GPIb␣ in detergent extracts of platelets. Three separate preparations of CVX (two purified by the authors; one obtained commercially) produced equivalent results. These results indicate that CVX exhibits dual specificity for both native GPIb␣ and GPVI. Furthermore, the binding site on GPIb␣ for CVX may be close to that for von Willebrand factor. Therefore, a contribution of GPIb␣ to CVX-induced platelet responses needs to be carefully re-evaluated.Convulxin (CVX) 1 is a 72-kDa protein from Crotalus durissus terrificus venom that has been shown to bind strongly to the platelet-specific collagen receptor, glycoprotein VI (GPVI) (1, 2).The active protein is composed of two disulfide-linked subunits, CVX␣ (13.9 kDa) and CVX␤ (12.6 kDa), which noncovalently assemble into a tridimeric complex (␣ ␤) 3 (3). Both subunits have been cloned and sequenced and exhibit homology with the carbohydrate recognition domain of C-type lectins (4, 5).C-type snake proteins are produced in the venom of numerous true vipers and pit vipers (5). They can be composed of homodimers or heterodimers, often present in multiples, each subunit exhibiting homology to the carbohydrate recognition domain of C-type lectins. Unlike the C-type lectins, however, the subunits of the heterodimeric C-type proteins, such as CVX, do not retain the mannose or galactose recognition sequences and, thus, no longer bind carbohydrate. The ability to bind calcium is retained and may be critical for their activity.A number of the C-type viper venom proteins target platelet receptors, including the glycoprotein Ib (GPIb) complex and GPVI. The majority, including alboaggregin A (6) and alboluxin (7), exhibit dual specificity for these receptors, whereas only...

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Ristocetin-dependent, but not botrocetin-dependent, binding of von Willebrand factor to the platelet glycoprotein Ib-IX-V complex correlates with shear-dependent interactions

Cited by 132 publications

References 38 publications

Tyrosine Sulfation of Glycoprotein Ibα

Tyrosine Sulfation of Glycoprotein Ibα

Specific inhibition of P-selectin–mediated cell adhesion by phage display–derived peptide antagonists

Convulxin Binds to Native, Human Glycoprotein Ibα

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