Title: Von Willebrand factor but not α-thrombin bonding to platelet glycoprotein Ibα is influenced by the HPA-2 polymorphism
Authors: Ulrichts, Hans ×
Vanhoorelbeke, Karen
Cauwenberghs, Sandra
Vauterin, Stephan
Kroll, Hartmut
Santoso, Sentot
Deckmyn, Hans #
Issue Date: Jul-2003
Publisher: Lippincott williams & wilkins
Series Title: Arteriosclerosis, Thrombosis and Vascular Biology vol:23 issue:7 pages:1302-1307
Abstract: OBJECTIVE: Glycoprotein (GP) Ibalpha is the functionally dominant subunit of the platelet GPIb-IX-V receptor complex. The N-terminal domain of the GPIbalpha chain contains binding sites for alpha-thrombin and von Willebrand factor (VWF). The human platelet alloantigen (HPA)-2 polymorphism of the GPIbalpha gene is associated with a C/T transition at nucleotide 1018, resulting in a Thr/Met dimorphism at residue 145 of GPIbalpha. To study the structural and functional effects of this dimorphism, N-terminal fragments (AA1-289) of the HPA-2a and HPA-2b alloform of GPIbalpha expressed in CHO cells were used. METHODS AND RESULTS: Of 74 moAbs directed against human GPIbalpha, 2 antibodies with epitope between AA1-59 could differentiate between both alloforms. In addition, VWF bound with a higher affinity to the recombinant HPA-2a fragment or to homozygous HPA-2a platelets. In contrast, no difference was found in the binding of alpha-thrombin to the recombinant alloform fragments or of antibodies directed against the alpha-thrombin binding anionic sulfated tyrosine sequence (AA269-282). CONCLUSIONS: Whereas the Thr145Met dimorphism does not affect alpha-thrombin binding, it does influence the conformation of the N-terminal flanking region and first leucine-rich repeat of GPIbalpha and by this has an effect on VWF binding.
ISSN: 1079-5642
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Chemistry, Campus Kulak Kortrijk
Interdisciplinary Research Facility Life Sciences, Campus Kulak Kortrijk
× corresponding author
# (joint) last author

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