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Crystallographic insight into collagen recognition by discoidin domain receptor 2.

Carafoli F, Bihan D, Stathopoulos S, Konitsiotis AD, Kvansakul M, Farndale RW, Leitinger B, Hohenester E - Structure (2009)

Bottom Line: We have determined the crystal structure of the discoidin domain of human DDR2 bound to a triple-helical collagen peptide.Collagen binding results in structural changes of DDR2 surface loops that may be linked to the process of receptor activation.A comparison of the GVMGFO-binding sites of DDR2 and SPARC reveals a striking case of convergent evolution in collagen recognition.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

ABSTRACT
The discoidin domain receptors, DDR1 and DDR2, are widely expressed receptor tyrosine kinases that are activated by triple-helical collagen. They control important aspects of cell behavior and are dysregulated in several human diseases. The major DDR2-binding site in collagens I-III is a GVMGFO motif (O is hydroxyproline) that also binds the matricellular protein SPARC. We have determined the crystal structure of the discoidin domain of human DDR2 bound to a triple-helical collagen peptide. The GVMGFO motifs of two collagen chains are recognized by an amphiphilic pocket delimited by a functionally critical tryptophan residue and a buried salt bridge. Collagen binding results in structural changes of DDR2 surface loops that may be linked to the process of receptor activation. A comparison of the GVMGFO-binding sites of DDR2 and SPARC reveals a striking case of convergent evolution in collagen recognition.

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Helix Parameters of the Collagen PeptideResidues [i–1 (leading), i (middle), i+1 (trailing)] were fitted to residues [i (leading), i+1 (middle), i+2 (trailing)], and the associated rotation was taken as the helical twist at position i. The sequence of the collagen peptide is indicated at the bottom. X denotes norleucine. The twists of ideal left-handed 7/2 and 10/3 helices are −103° and −108°, respectively (Okuyama et al., 2006).
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fig3: Helix Parameters of the Collagen PeptideResidues [i–1 (leading), i (middle), i+1 (trailing)] were fitted to residues [i (leading), i+1 (middle), i+2 (trailing)], and the associated rotation was taken as the helical twist at position i. The sequence of the collagen peptide is indicated at the bottom. X denotes norleucine. The twists of ideal left-handed 7/2 and 10/3 helices are −103° and −108°, respectively (Okuyama et al., 2006).

Mentions: The collagen peptide in the DDR2 DS-collagen complex is completely straight (Figure 2B), and the helical parameters of the three collagen chains are therefore essentially identical. The GPO-rich N-terminal region is close to a 7/2 helical symmetry, whereas the GVNleGFO motif approximates a more relaxed 10/3 symmetry (Figure 3). A relaxation of the helical twist in regions lacking imino acids has been observed in several model peptide structures (Kramer et al., 1999; Okuyama et al., 2006). The observed transition in helix parameters is thus likely to be an inherent feature of the collagen peptide itself, rather than a consequence of DDR2 binding.


Crystallographic insight into collagen recognition by discoidin domain receptor 2.

Carafoli F, Bihan D, Stathopoulos S, Konitsiotis AD, Kvansakul M, Farndale RW, Leitinger B, Hohenester E - Structure (2009)

Helix Parameters of the Collagen PeptideResidues [i–1 (leading), i (middle), i+1 (trailing)] were fitted to residues [i (leading), i+1 (middle), i+2 (trailing)], and the associated rotation was taken as the helical twist at position i. The sequence of the collagen peptide is indicated at the bottom. X denotes norleucine. The twists of ideal left-handed 7/2 and 10/3 helices are −103° and −108°, respectively (Okuyama et al., 2006).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2807035&req=5

fig3: Helix Parameters of the Collagen PeptideResidues [i–1 (leading), i (middle), i+1 (trailing)] were fitted to residues [i (leading), i+1 (middle), i+2 (trailing)], and the associated rotation was taken as the helical twist at position i. The sequence of the collagen peptide is indicated at the bottom. X denotes norleucine. The twists of ideal left-handed 7/2 and 10/3 helices are −103° and −108°, respectively (Okuyama et al., 2006).
Mentions: The collagen peptide in the DDR2 DS-collagen complex is completely straight (Figure 2B), and the helical parameters of the three collagen chains are therefore essentially identical. The GPO-rich N-terminal region is close to a 7/2 helical symmetry, whereas the GVNleGFO motif approximates a more relaxed 10/3 symmetry (Figure 3). A relaxation of the helical twist in regions lacking imino acids has been observed in several model peptide structures (Kramer et al., 1999; Okuyama et al., 2006). The observed transition in helix parameters is thus likely to be an inherent feature of the collagen peptide itself, rather than a consequence of DDR2 binding.

Bottom Line: We have determined the crystal structure of the discoidin domain of human DDR2 bound to a triple-helical collagen peptide.Collagen binding results in structural changes of DDR2 surface loops that may be linked to the process of receptor activation.A comparison of the GVMGFO-binding sites of DDR2 and SPARC reveals a striking case of convergent evolution in collagen recognition.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

ABSTRACT
The discoidin domain receptors, DDR1 and DDR2, are widely expressed receptor tyrosine kinases that are activated by triple-helical collagen. They control important aspects of cell behavior and are dysregulated in several human diseases. The major DDR2-binding site in collagens I-III is a GVMGFO motif (O is hydroxyproline) that also binds the matricellular protein SPARC. We have determined the crystal structure of the discoidin domain of human DDR2 bound to a triple-helical collagen peptide. The GVMGFO motifs of two collagen chains are recognized by an amphiphilic pocket delimited by a functionally critical tryptophan residue and a buried salt bridge. Collagen binding results in structural changes of DDR2 surface loops that may be linked to the process of receptor activation. A comparison of the GVMGFO-binding sites of DDR2 and SPARC reveals a striking case of convergent evolution in collagen recognition.

Show MeSH