Collagen-binding mode of vWF-A3 domain determined by a transferred cross-saturation experiment

Nishida, N.; Sumikawa, Hiromi; Sakakura, Masayoshi; Shimba, Nobuhisa; Takahashi, Hideo; Terasawa, Hiroaki; Suzuki, E; Shimada, Ichio

doi:10.1038/nsb876

Cited by 72 publications

(76 citation statements)

References 31 publications

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“…Apparently, the introduction of a much larger histidine side chain at this position blocks the binding of 82D6A3 and A3 by steric hindrance. However, Nishida et al (32) reported an important decrease in collagen binding of the P982A mutant, but they used isolated A3-domain mutants, whereas we expressed the full-length VWF protein. Apart from the P981H mutation, mutation of Arg 963 , Asp 1009 , Arg 1016 , Ser 1020 , Met 1022 , and His 1023 to alanine also affected 82D6A3 binding with R963A, R1016A, S1020A, and H1023A previously reported to result in a reduced collagen binding (30,31).…”

Section: Discussionmentioning

confidence: 99%

A Consensus Tetrapeptide Selected by Phage Display Adopts the Conformation of a Dominant Discontinuous Epitope of a Monoclonal Anti-VWF Antibody That Inhibits the von Willebrand Factor-Collagen Interaction

Vanhoorelbeke

Depraetere

Romijn

et al. 2003

Journal of Biological Chemistry

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Monoclonal antibody (mAb) 82D6A3 is an anti-vonIn conclusion, to our knowledge, this is the first report where a modeled peptide containing a consensus sequence could be fitted onto the three-dimensional structure of the antigen, indicating that it might adopt the conformation of the discontinuous epitope.Platelet adhesion to subendothelial structures, more specifically to the thrombogenic compound collagen, is one of the first steps in a sequence of reactions that can lead to arterial thrombosis. Platelets interact with collagen both in a direct manner via their collagen receptors (e.g. ␣ 2 ␤ 1 (1, 2) and glycoproteins IV (3) and VI (4, 5)) and indirectly with VWF, 1 forming the bridge between collagen and its platelet receptor glycoprotein Ib/IX/V (6). Binding via both ␣ 2 ␤ 1 and VWF is necessary to sustain platelet adhesion under high shear forces (7-9); VWF-mediated interaction results in rolling of the platelets over the collagen surface (10), upon which the collagen receptors can interact with the damaged vessel wall, leading to firm adhesion. This is the result of platelet activation by the signal-transducing glycoprotein VI (11), leading to a gain-in-affinity of ␣ 2 ␤ 1 (12) and activation of ␣ IIb ␤ 3 with platelet aggregation as a consequence.Both ␣ 2 ␤ 1 and VWF bind to collagen through their I-domains, in VWF known as A-domains (13-19). A-domains form independent globular modules of some 200 amino acid residues. In VWF three such domains have been identified. The A1-domain contains the binding site for glycoprotein Ib (20,21), sulfatides (22), heparin (23), and collagen VI (24, 25), which constitutes the main reactive collagen in the extracellular matrix of endothelial cells. The A2-domain has no clear binding function but is sensitive to protease ADAMTS13-mediated enzymatic degradation (26,27), whereas the A3-domain (residues 920 -1111) contains the main binding site for fibrillar collagens such as type I and III (19,28). Recombinant A3-domain also binds to collagen (28), whereas deletion of A3 results in a VWF that binds 40 times less to collagen (19). By using synthetic triple helical collagen-related peptides, the VWF-binding site has been localized to residues 541-558 of the ␣1CB4(III) fragment of collagen type III (29). Recently, we identified the collagen binding site by cocrystallization of the A3-domain with an inhibitory anti-A3 antibody, RU5, which was confirmed by showing that especially an H1023A mutant abolished binding of VWF to collagen (30). This study was further extended by the analysis of a series of 27 VWF-A3 mutants, which defined the collagen binding site of the VWF-A3-domain to the "front" face of the domain (31), an observation confirmed by Nishida et al. (32).We raised a monoclonal antibody (mAb), 82D6A3, against human VWF that prevents the binding of VWF to collagen (24) and that is antithrombotic in a baboon arterial thrombosis model (33). Since a previous effort to determine the epitope of 82D6A3 using phage display, was not successful (34, 35), we repeated this study us...

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Section: Discussionmentioning

confidence: 99%

A Consensus Tetrapeptide Selected by Phage Display Adopts the Conformation of a Dominant Discontinuous Epitope of a Monoclonal Anti-VWF Antibody That Inhibits the von Willebrand Factor-Collagen Interaction

Vanhoorelbeke

Depraetere

Romijn

et al. 2003

Journal of Biological Chemistry

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“…After submission of this manuscript, Nishida et al (35) reported mapping of the collagen-binding site of the VWF-A3 domain using a novel NMR technique. Their findings with regard to the location of the binding site and the orientation of a bound collagen triple helix are in complete agreement with our results.…”

Section: Discussionmentioning

confidence: 99%

Mapping the Collagen-binding Site in the von Willebrand Factor-A3 Domain

Romijn

Westein

Bouma

et al. 2003

Journal of Biological Chemistry

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The multimeric glycoprotein von Willebrand factor (VWF) mediates platelet adhesion to collagen at sites of vascular damage. The binding site for collagen types I and III is located in the VWF-A3 domain. Recently, we showed that His 1023 , located near the edge between the "front" and "bottom" faces of A3, is critical for collagen binding (Romijn, R. A., Bouma, B., Wuyster, W., Gros, P., Kroon, J., Sixma, J. J., and Huizinga, E. G. (2001) reduced binding affinity about 10-fold. Together, these residues define a flat and rather hydrophobic collagenbinding site located at the front face of the A3 domain. The collagen-binding site of VWF-A3 is distinctly different from that of the homologous integrin ␣ 2 I domain, which has a hydrophilic binding site located at the top face of the domain. Based on the surface characteristics of the collagen-binding site of A3, we propose that it interacts with collagen sequences containing positively charged and hydrophobic residues. Docking of a collagen triple helix on the binding site suggests a range of possible engagements and predicts that at most eight consecutive residues in a collagen triple helix interact with A3.Under conditions of high shear stress, platelet adhesion to collagen at sites of vascular injury is initiated by the interaction of platelet receptor glycoprotein (Gp) 1 Ib-IX-V with collagen-bound von Willebrand factor (VWF) (1). Transient interactions between VWF and GpIb-IX-V mediate platelet rolling, which slows down the platelet and allows other platelet receptors such as integrin ␣ 2 ␤ 1 (2) and GpVI to bind to collagen (2-4). These interactions result in firm adhesion and activation of platelets at the site of vascular injury.VWF is a multimeric glycoprotein consisting of ϳ270-kDa monomers that are linked by disulfide bonds (5). The affinity of VWF for collagen depends on multimer size (6). The binding site for fibrillar collagens type I and III is located in the VWF-A3 domain (7), whereas collagen type VI has been shown to bind to the VWF-A1 domain (8, 9). The latter domain also contains the binding site for GpIb␣ of the GpIb-IX-V complex (10, 11).VWF A-type domains and homologous integrin I domains adopt a so-called dinucleotide-binding fold, or Rossman fold, composed of a central ␤-sheet flanked on both sides by amphipathic ␣-helices (12-15). Binding of the I domains of integrins ␣ 1 ␤ 1 , ␣ 2 ␤ 1 , ␣ 10 ␤ 1 , and ␣ 11 ␤ 1 to collagen involves a divalent cation (16, 17) located in the metal ion-dependent adhesion site (MIDAS) motif, and amino acid residues at the top face of the domain (18,19). Binding of the I domain of integrin ␣ 2 ␤ 1 to collagen induces a major displacement of its carboxyl-terminal ␣-helix that is thought to be critical for integrin signaling (18). The A3 domain of VWF does not contain a functional MIDAS motif, and binding of A3 to collagen is cation-independent (20, 21). The involvement of the top face of A3 in collagen binding has been excluded by mutagenesis studies (13,22). Recently, we showed that His 1023 , located close to th...

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“…The collagen-binding A3 domain of VWF has been crystallized and its collagen binding site mapped by NMR, antibody blocking and mutagenesis experiments (35)(36)(37)(38). The collagenbinding site delineated by these studies is a shallow groove, with no obvious Phe pocket.…”

Section: Prediction Of Sparc-binding Sites In Collagens I-ivmentioning

confidence: 99%

Structural basis of sequence-specific collagen recognition by SPARC

Hohenester

Sasaki

Giudici

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

124

115

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Protein interactions with the collagen triple helix play a critical role in collagen fibril formation, cell adhesion, and signaling. However, structural insight into sequence-specific collagen recognition is limited to an integrin-peptide complex. A GVMGFO motif in fibrillar collagens (O denotes 4-hydroxyproline) binds 3 unrelated proteins: von Willebrand factor (VWF), discoidin domain receptor 2 (DDR2), and the extracellular matrix protein SPARC/osteonectin/BM-40. We report the crystal structure at 3.2 Å resolution of human SPARC bound to a triple-helical 33-residue peptide harboring the promiscuous GVMGFO motif. SPARC recognizes the GVMGFO motifs of the middle and trailing collagen chains, burying a total of 720 Å 2 of solvent-accessible collagen surface. SPARC binding does not distort the canonical triple helix of the collagen peptide. In contrast, a critical loop in SPARC is substantially remodelled upon collagen binding, creating a deep pocket that accommodates the phenylalanine residue of the trailing collagen chain (''Phe pocket''). This highly restrictive specificity pocket is shared with the collagenbinding integrin I-domains but differs strikingly from the shallow collagen-binding grooves of the platelet receptor glycoprotein VI and microbial adhesins. We speculate that binding of the GVMGFO motif to VWF and DDR2 also results in structural changes and the formation of a Phe pocket. extracellular matrix ͉ X-ray crystallography C ollagen, the most abundant protein in vertebrates, is characterized by a triple-helical structure of 3 polypeptide chains containing repetitive glycine-X-XЈ triplets; the X and XЈ positions, respectively, are often occupied by the imino acids proline and 4-hydroxyproline (O). The 28 human collagens have numerous essential functions in tissue formation, stability and homeostasis, and mutations in collagen genes cause many human diseases (1). Collagens I-III, V and XI form supramolecular fibrils that lend mechanical stability to the vertebrate body. Normal collagen fibrillogenesis in vivo requires a number of globular proteins interacting with the triple helix, such as small leucine-rich repeat proteoglycans (2). Cellular interactions with collagen are mediated by a diverse group of transmembrane collagen receptors, including integrins, discoidin domain receptors (DDRs) and members of the Ig superfamily (3-5). Although the structure of the collagen triple helix has been known for Ͼ50 years (6), protein-collagen interactions remain poorly understood at the atomic level.Synthetic triple-helical peptides have been invaluable in mapping specific binding sites within collagen (7). The major integrin-binding site in fibrillar collagens I and II is a GFOGER motif (8, 9). The atomic details of this important interaction were revealed by a crystal structure of the integrin ␣2 I-domain bound to a 21-residue triple helical peptide, providing the only example to date of a vertebrate protein-collagen complex (10). More recent studies have identified a GVMGFO motif, conserved in collagens I-III...

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Collagen-binding mode of vWF-A3 domain determined by a transferred cross-saturation experiment

Cited by 72 publications

References 31 publications

A Consensus Tetrapeptide Selected by Phage Display Adopts the Conformation of a Dominant Discontinuous Epitope of a Monoclonal Anti-VWF Antibody That Inhibits the von Willebrand Factor-Collagen Interaction

A Consensus Tetrapeptide Selected by Phage Display Adopts the Conformation of a Dominant Discontinuous Epitope of a Monoclonal Anti-VWF Antibody That Inhibits the von Willebrand Factor-Collagen Interaction

Mapping the Collagen-binding Site in the von Willebrand Factor-A3 Domain

Structural basis of sequence-specific collagen recognition by SPARC

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