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首页> 外文期刊>Infection and immunity >First Analysis of a Bacterial Collagen-Binding Protein with Collagen Toolkits: Promiscuous Binding of YadA to Collagens May Explain How YadA Interferes with Host Processes
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First Analysis of a Bacterial Collagen-Binding Protein with Collagen Toolkits: Promiscuous Binding of YadA to Collagens May Explain How YadA Interferes with Host Processes

机译：使用胶原蛋白工具包对细菌胶原蛋白结合蛋白进行的首次分析：YadA与胶原蛋白的混杂结合可能说明YadA如何干扰宿主过程

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The Yersinia adhesin YadA mediates the adhesion of the human enteropathogen Yersinia enterocolitica to collagens and other components of the extracellular matrix. Though YadA has been proposed to bind to a specific site in collagens, the exact binding determinants for YadA in native collagen have not previously been elucidated. We investigated the binding of YadA to collagen Toolkits, which are libraries of triple-helical peptides spanning the sequences of type II and III human collagens. YadA bound to many of them, in particular to peptides rich in hydroxyproline but with few charged residues. We were able to block the binding of YadA to collagen type IV with the triple-helical peptide (Pro-Hyp-Gly)10, suggesting that the same site in YadA binds to triple-helical regions in network-forming collagens as well. We showed that a single Gly-Pro-Hyp triplet in a triple-helical peptide was sufficient to support YadA binding, but more than six triplets were required to form a tight YadA binding site. This is significantly longer than the case for eukaryotic collagen-binding proteins. YadA-expressing bacteria bound promiscuously to Toolkit peptides. Promiscuous binding could be advantageous for pathogenicity in Y. enterocolitica and, indeed, for other pathogenic bacteria. Many of the tightly binding peptides are also targets for eukaryotic collagen-binding proteins, and YadA was able to inhibit the interaction between selected Toolkit peptides and platelets. This leads to the intriguing possibility that YadA may interfere in vivo with host processes mediated by endogenous collagen-binding proteins.
机译：耶尔森氏菌粘附素YadA介导人肠病原小肠结肠炎耶尔森菌对胶原蛋白和细胞外基质的其他成分的粘附。尽管已提出YadA结合胶原蛋白中的特定位点，但以前尚未阐明天然胶原蛋白中YadA的确切结合决定因素。我们研究了YadA与胶原蛋白工具包的结合，胶原蛋白工具包是跨越II型和III型人类胶原蛋白序列的三螺旋肽文库。 YadA与许多肽结合，特别是与富含羟脯氨酸但带电荷的残基很少的肽结合。我们能够用三螺旋肽（Pro-Hyp-Gly）10阻断YadA与IV型胶原蛋白的结合，这表明YadA中的相同位点也与网络形成胶原蛋白中的三螺旋区结合。我们表明，三螺旋肽中的单个Gly-Pro-Hyp三联体足以支持YadA结合，但是需要六个以上的三联体才能形成紧密的YadA结合位点。这明显长于真核胶原结合蛋白的情况。表达YadA的细菌与Toolkit肽混杂结合。混杂结合对于肠小肠结肠炎耶尔森氏菌（Y.enterocolitica）中的致病性可能有益，而对其他致病性细菌的确如此。许多紧密结合的肽也是真核胶原结合蛋白的靶标，并且YadA能够抑制所选Toolkit肽与血小板之间的相互作用。这导致YadA可能在体内干扰由内源性胶原结合蛋白介导的宿主过程的可能性。

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