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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Implications for collagen I chain registry from the structure of the collagen von Willebrand factor A3 domain complex
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Implications for collagen I chain registry from the structure of the collagen von Willebrand factor A3 domain complex

机译：胶原von Willebrand因子A3结构域复合物的结构对胶原I链注册表的影响

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摘要

Fibrillar collagens, the most abundant proteins in the vertebrate body, are involved in a plethora of biological interactions. Plasma protein von Willebrand factor (VWF) mediates adhesion of blood platelets to fibrillar collagen types Ⅰ , Ⅱ , and Ⅲ, which is essential for normal haemostasis. High affinity VWF-binding sequences have been identified in the homotrimeric collagen types Ⅱ and Ⅲ, however, it is unclear how VWF recognizes the heterotrimeric collagen type Ⅰ, the superstructure of which is unknown. Here we present the crystal structure of VWF domain A3 bound to a collagen type Ill-derived homotrimeric peptide. Our structure reveals that VWF-A3 interacts with all three collagen chains and binds through conformational selection to a sequence that is one triplet longer than was previously appreciated from platelet and VWF binding studies. The VWF-binding site overlaps those of SPARC (also known as osteonectin) and discodin domain receptor 2, but is more extended and shifted toward the collagen amino terminus. The observed collagen-binding mode of VWF-A3 provides direct structural constraints on collagen I chain registry. A VWF-binding site can be generated from the sequences RGQAGVMF, present in the two α1 (Ⅰ) chains, and RGEOGNIGF, in the unique α2(Ⅰ) chain, provided that α2(Ⅰ) is in the middle or trailing position. Combining these data with previous structural data on integrin binding to collagen yields strong support for the trailing position of the α2(Ⅰ) chain, shedding light on the fundamental and long-standing question of the collagen I chain registry.
机译：纤维状胶原蛋白是脊椎动物体内最丰富的蛋白质，与多种生物相互作用有关。血浆蛋白von Willebrand因子（VWF）介导血小板与Ⅰ，Ⅱ和Ⅲ型胶原纤维的粘附，这对于正常止血至关重要。在Ⅱ型和Ⅲ型三聚体胶原中已鉴定出高亲和力的VWF结合序列，但是，尚不清楚VWF如何识别Ⅰ型的异源三聚体胶原，其上部结构未知。在这里，我们介绍VWF域A3的晶体结构，该结构结合到III型胶原衍生的同源三聚体肽上。我们的结构表明，VWF-A3与所有三个胶原链相互作用，并通过构象选择与比血小板和VWF结合研究以前所见的序列长三倍的序列结合。 VWF结合位点与SPARC（也称为骨连接蛋白）和Discodin域受体2的结合位点重叠，但更延伸并移向胶原蛋白氨基末端。观察到的VWF-A3胶原结合模式对胶原I链注册表提供了直接的结构限制。可以从存在于两条α1（Ⅰ）链中的序列RGQAGVMF和位于唯一α2（Ⅰ）链中的RGEOGNIGF产生一个VWF结合位点，前提是α2（Ⅰ）位于中间或尾随位置。将这些数据与整合素与胶原蛋白结合的先前结构数据相结合，为α2（Ⅰ）链的尾部位置提供了有力的支持，这为胶原蛋白I链配体的基本和长期存在的问题提供了线索。

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    T. Harma C. Brondijk; Dominique Bihan; Richard W. Farndale; Eric G. Huizinga;

  • 作者单位

    Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands;

    Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom;

    Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom;

    Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    X-ray crystallography; extracellular matrix;

    机译：X射线晶体学;细胞外基质;

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