Identification of multiple potent binding sites for human leukocyte associated Ig-like receptor LAIR on collagens II and III

Lebbink, Robert Jan; Raynal, Nicolas; Ruiter, Talitha de; Bihan, Dominique; Farndale, Richard W.; Meyaard, Linde

doi:10.1016/j.matbio.2009.03.005

Cited by 90 publications

(121 citation statements)

References 32 publications

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“…The binding of a number of eukaryotic proteins to the Toolkits has been studied previously, including that of integrin ␣ 2 ␤ 1 , von Willebrand factor, DDR2, SPARC, and GpVI (reviewed in reference 14). Recently, the binding of LAIR-1 and -2 to the Toolkits was investigated (29). In all of these cases, the proteins clearly bound to a single or just a few peptides, and the Toolkit peptides could be grouped unambiguously into two populations, binders and nonbinders.…”

Section: Discussionmentioning

confidence: 99%

“…YadA binds well to a number of peptides that contain binding sites for eukaryotic collagen-binding proteins. For example, the leukocyte-associated Ig-like receptors (LAIRs) 1 and 2 bind peptides II-56, III-1, and III-30 (29), and discoidin domain receptor 2 (DDR2) binds peptides II-13, II-22, and II-44 (28), which are all strong-or intermediateaffinity ligands for YadA. Platelet deposition upon collagenous substrates depends upon three receptors, namely, integrin ␣ 2 ␤ 1 , the activating receptor glycoprotein VI (GpVI), and GpIb, which binds to the von Willebrand factor (VWF) A1 domain, while in turn, the VWF A3 domain binds a single site in collagens (31).…”

Section: Binding Of Yada To Fibrous and Network-forming Collagensmentioning

confidence: 99%

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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

et al. 2010

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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 collagenbinding 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.

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Section: Discussionmentioning

confidence: 99%

Section: Binding Of Yada To Fibrous and Network-forming Collagensmentioning

confidence: 99%

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

et al. 2010

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“…11 Recently, collagen-binding properties of GPVI and LAIR-1 have been characterized using collagen II-and collagen III-derived synthetic Toolkit peptides. 7,12 LAIR-1 appears to have several binding sites on collagens II and III and its binding spectrum on the latter is overlapping, although not identical, with that of GPVI. 13 LAIR-1 and GPVI are structurally related to several other inhibitory and activating LRC receptors.…”

Section: Introductionmentioning

confidence: 93%

“…2 LAIR-1 binds both transmembrane and extracellular matrix collagens. 6,7 Under physiologic conditions, immune cells present in the bloodstream do not encounter matrix collagens. However, their extravasion results in exposure to the collagen-rich subendothelium, where LAIR-1 transduces an inhibitory signal to the cell, resulting in abrogation or inhibition of immune cell function.…”

Section: Introductionmentioning

confidence: 99%

Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI

Brondijk

Ruiter

Ballering

et al. 2010

Blood

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Leukocyte-associated immunoglobulinlike receptor-1 (LAIR-1), one of the most widely spread immune receptors, attenuates immune cell activation when bound to specific sites in collagen. The collagenbinding domain of LAIR-1 is homologous to that of glycoprotein VI (GPVI), a collagen receptor crucial for platelet activation. Because LAIR-1 and GPVI also display overlapping collagen-binding specificities, a common structural basis for collagen recognition would appear likely. Therefore, it is crucial to gain insight into the molecular interaction of both receptors with their ligand to prevent unwanted cross-reactions during therapeutic intervention. We determined the crystal structure of LAIR-1 and mapped its collagen-binding site by nuclear magnetic resonance (NMR) titrations and mutagenesis. Our data identify R59, E61, and W109 as key residues for collagen interaction. These residues are strictly conserved in LAIR-1 and GPVI alike; however, they are located outside the previously proposed GPVI collagenbinding site. Our data provide evidence for an unanticipated mechanism of collagen recognition common to LAIR-1 and GPVI. This fundamental insight will contribute to the exploration of specific means of intervention in collagen-induced signaling in immunity and hemostasis. (Blood.

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“…8 This is the only inhibitory receptor described so far that binds collagen and the collagen-binding site in LAIR-1 and GPVI overlaps between the two receptors. [19][20][21] In collaboration with our group, Tomlinson et al showed that when both receptors are ectopically expressed on the same cell, LAIR-1 cross-linking abrogates collagen-induced GPVI-signaling. 22 Co-expression of both receptor types on primary cells would, therefore, potentially affect their responsiveness to collagen.…”

Section: Introductionmentioning

confidence: 99%

Co-expression of the collagen receptors leukocyte-associated immunoglobulin-like receptor-1 and glycoprotein VI on a subset of megakaryoblasts

Steevels

Westerlaken²,

Tijssen³

et al. 2010

Haematologica

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Identification of multiple potent binding sites for human leukocyte associated Ig-like receptor LAIR on collagens II and III

Cited by 90 publications

References 32 publications

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

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

Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI

Co-expression of the collagen receptors leukocyte-associated immunoglobulin-like receptor-1 and glycoprotein VI on a subset of megakaryoblasts

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