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Platelet Glycoprotein Ib (platelet + glycoprotein_ib)
Selected AbstractsExpression of low-frequency Ala108Pro substitution in the platelet glycoprotein Ib, geneINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2003S. Kunishima Summary We determined the gene frequency of the glycoprotein (GP) Ib, Ala108Pro substitution. The Pro108 allele was not found in 208 healthy Japanese and 200 healthy Caucasians. In vitro expression studies showed surface expression of the GPIb, Pro108 variant, suggesting the possibility of the involvement of the substitution as an alloantigen. [source] Variable number of tandem repeats polymorphism of platelet glycoprotein Ib , in Chinese people and CC genotype with aspirin sensitivity in patients with cerebral infarctionJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2009Y.-Y. Jin MM Summary Background and objective:, To study the prevalence of variable number of tandem repeats (VNTR) polymorphism in platelet membrane glycoprotein (GP) Ib , in a Chinese Han population and to determine the relationship between VNTR polymorphisms and aspirin resistance. Methods:, Three hundred healthy individuals and 110 patients with cerebral infarction volunteered to participate in this study. The genotype status of all participants was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Platelet aggregation in patients with cerebral infarction receiving aspirin (100 mg/day) for at least 7 days, was measured by optical transmission aggregometry. Results and discussion:, Only three alleles of GP Ib ,, namely, B, C and D, were found. Type A was not found in the Chinese Han participants. Aspirin-sensitive patients were significantly more often of CC genotype than aspirin-semi-responders. Conclusions:, Only three types of alleles B, C and D were detected in the north-eastern region of China. The CC genotype of the VTNR polymorphism in GPIb appears to be more sensitive to the inhibitory action of low-dose aspirin. [source] Binding of platelet glycoprotein Ib, through the convex surface of leucine-rich repeats domain of glycoprotein IXJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2009X. MO Summary.,Background: The mechanism of assembly of the platelet glycoprotein (GP) Ib-IX complex from GPIb,, GPIb, and GPIX subunits is not entirely clear. In this complex, ectodomains of both GPIb, and GPIX subunits contain two leucine-rich repeats (LRR) and share high sequence similarity. However, they differ noticeably in stability, hampering further analysis of their interaction. Objectives and methods: Guided by analysis of the LRR structure, we report a well-folded Ib,/IX chimera and its usage in dissecting GPIX function. Results: In this chimera, three non-contiguous sequences that may constitute the putative convex surface of the GPIb, ectodomain are replaced by their GPIX counterparts. Like GPIb, but unlike GPIX ectodomain, it can secrete from transfected Chinese hamster ovary cells and fold into a stable conformation. Furthermore, replacing the ectodomain in GPIX with the Ib,/IX chimera, but not the GPIb, ectodomain, preserved its interaction with GPIb, as demonstrated by its native-like GPIb,-induced increase in surface expression and coimmunoprecipitation. Conclusions: The putative convex surface of the LRR domain in GPIX is sufficient, in the context of full-length subunit, to mediate its association with GPIb,. [source] Purified A2 domain of von Willebrand factor binds to the active conformation of von Willebrand factor and blocks the interaction with platelet glycoprotein Ib,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2007C. MARTIN Summary.,Background:,von Willebrand factor (VWF) does not interact with circulating platelets unless it is induced to expose the binding site for platelet glycoprotein (GP)Ib, in the A1 domain by high shear stress, immobilization, and/or a modulator. Previous studies have implied indirectly that the A2 domain may be involved in regulating A1,GPIb, binding. Objective and methods:,Because the relationship between the A1 and A2 domains has not been defined, we have investigated the effect of the A2 domain on the binding activity of the A1 domain using recombinant A domain polypeptides, multimeric VWF, and monoclonal antibodies (mAb). Results:,The A2 domain polypeptide bound specifically to the immobilized A1 domain polypeptide or full-length VWF, with half-maximal binding being obtained at 60 or 168 nm, respectively. This A1,A2 interaction was inhibited by mAb against the A2 or A1 domain and by the A1 domain polypeptide. The A2 domain polypeptide effectively blocked GPIb,-mediated platelet adhesion under high flow conditions. The A2 domain polypeptide specifically recognizes the GPIb,-binding conformation in the A1 domain, as it only interacted with VWF activated by the modulator ristocetin or immobilized VWF. Furthermore, in contrast to plasma VWF, the ultra-large (UL)VWF multimers or a recombinant VWF,A1A2A3 polypeptide containing a gain-of-function mutation (R1308 L) of type 2B von Willebrand disease bound to the A2 domain polypeptide without the need for ristocetin. Conclusions:,The recombinant A2 domain polypeptide specifically binds to the active conformation of the A1 domain in VWF and effectively blocks the interaction with platelet GPIb, under high-flow conditions. [source] Expression studies on a novel type 2B variant of the von Willebrand factor gene (R1308L) characterized by defective collagen bindingJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2005L. BARONCIANI Summary., A novel mutation, R1308L (3923G > T) was present in the heterozygous state in five members of a family with type 2B von Willebrand disease (VWD) characterized by a full set of von Willebrand factor (VWF) multimers in plasma and by the absence of thrombocytopenia before and after desmopressin (DDAVP). The defect (R1308L) was located at the same amino acid position of one of the most common mutations associated with type 2B VWD (R1308C), which is characterized by the loss of high molecular weight VWF multimers (HMWM) in plasma and the occurrence of thrombocytopenia. To understand the mechanisms of this defect, the novel (R1308L) and ,common' (R1308C) mutations were expressed in COS-7 cells, either alone or, to mimic the patients' heterozygous state, together with wild-type VWF. R1308L recombinant VWF (rVWF) had a higher affinity for the platelet glycoprotein Ib, (GPIb,) receptor than wild-type rVWF, R1308C rVWF showing an even higher affinity. A novel finding was that both mutant rVWFs showed a similarly reduced binding to collagen type I and type III in comparison with wild-type rVWF. The latter finding suggests a more important role than recognized so far for the VWF A1 domain in VWF binding to collagen, which may contribute to the in vivo hemostatic defect associated with type 2B VWD. [source] Platinum-induced space-group transformation in crystals of the platelet glycoprotein Ib, N-terminal domainACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2004Kottayil I. Varughese The interaction between platelet glycoprotein (GP) Ib, and von Willebrand factor (VWF) is essential for thrombus formation, leading to the arrest of bleeding. The N-terminal domain of GP Ib,, which contains the binding sites for VWF and ,-thrombin, crystallized in the tetragonal space group P43 with one molecule in the asymmetric unit. When the crystals were treated with platinum, the crystals changed their symmetry from tetragonal to monoclinic P21 with two molecules in the asymmetric unit. The structure of the monoclinic form was solved using two-wavelength platinum anomalous dispersion data. The tetragonal crystal structure was subsequently solved using molecular-replacement techniques using the monoclinic structure as the search model and was refined with 1.7,Å resolution data. [source] Crystallization and preliminary X-ray crystallographic analysis of agkicetin-C from Deinagkistrodon acutus venomACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2005Gufeng Xu The crystallization and preliminary crystallographic analysis of agkicetin-C, a well known platelet glycoprotein Ib (GPIb) antagonist from the venom of Deinagkistrodon acutus found in Anhui Province, China is reported. Crystals of agkicetin-C suitable for structure determination were obtained from 1.8,M ammonium sulfate, 40,mM MES pH 6.5 with 2%(v/v) PEG 400. Interestingly, low buffer concentrations of MES seem to be necessary for crystal growth. The crystals of agkicetin-C belong to space group C2, with unit-cell parameters a = 177.5, b = 97.7, c = 106.8,Å, , = 118.5°, and diffract to 2.4,Å resolution. Solution of the phase problem by the molecular-replacement method shows that there are four agkicetin-C molecules in the asymmetric unit, with a VM value of 3.4,Å3,Da,1, which corresponds to a high solvent content of approximately 64%. Self-rotation function calculations show a single well defined non-crystallographic twofold axis with features that may represent additional elements of non-crystallographic symmetry. [source] | |||||||||||||