Identification of a major GpVI-binding locus in human type III collagen.

Identification of a major GpVI-binding locus in human type III collagen.
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DOI:
10.1182/blood-2007-08-108472
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发表时间:
2008-05-15
期刊:
影响因子:
20.3
通讯作者:
Farndale RW
Farndale RW
中科院分区:
医学1区
文献类型:
--
作者:
Jarvis GE;Raynal N;Langford JP;Onley DJ;Andrews A;Smethurst PA;Farndale RW

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我们分析了人和鼠血小板以及重组人和鼠 GpVI 胞外域与合成三螺旋胶原蛋白样肽的粘附。其中包括源自人 III 型胶原蛋白序列的 57 种肽和源自牛 III 型胶原蛋白 α1(III)CB4 溴化氰片段的 9 种肽。我们已经鉴定了几种与 GpVI 相互作用的肽,特别是命名为 III-30 的肽,其序列为 GAOGLRGGAGPOGPEGGKGAAGPOGPO。人和鼠血小板均以 GpVI 依赖性方式与肽 III-30 结合。 III-30 还支持重组 GpVI 胞外域的结合。交联的 III-30 诱导人和鼠血小板聚集,但其效力低​​于胶原蛋白相关肽。肽序列的修饰表明羟脯氨酸残基在支持其 GpVI 反应性方面发挥着重要作用。然而,许多含有 OGP/GPO 基序的肽不支持与 GpVI 的粘附。这些数据表明三螺旋肽结合GpVI的能力不仅仅取决于肽内这些OGP/GPO基序的存在或空间排列。
We have analyzed the adhesion of human and murine platelets, and of recombinant human and murine GpVI ectodomains, to synthetic triple-helical collagen-like peptides. These included 57 peptides derived from the sequence of human type III collagen and 9 peptides derived from the cyanogen bromide fragment of bovine type III collagen, α1(III)CB4. We have identified several peptides that interact with GpVI, in particular a peptide designated III-30 with the sequence GAOGLRGGAGPOGPEGGKGAAGPOGPO. Both human and murine platelets bound to peptide III-30 in a GpVI-dependent manner. III-30 also supported binding of recombinant GpVI ectodomains. Cross-linked III-30 induced aggregation of human and murine platelets, although with a lower potency than collagen-related peptide. Modifications of the peptide sequence indicated that the hydroxyproline residues play a significant role in supporting its GpVI reactivity. However, many peptides containing OGP/GPO motifs did not support adhesion to GpVI. These data indicate that the ability of a triple-helical peptide to bind GpVI is not solely determined by the presence or spatial arrangement of these OGP/GPO motifs within the peptides.
DOI: 10.1038/sj.bjp.0705095
发表时间: 2003-02-01
影响因子: 7.3
作者:
Jarvis, GE;Atkinson, BT;Watson, SP
通讯作者: Watson, SP
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影响因子: 4.8
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发表时间: 1980-01-01
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DOI: 10.1182/blood-2006-03-011965
发表时间: 2006-12-01
期刊: BLOOD
影响因子: 20.3
作者:
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通讯作者: Farndale, Richard W.