J. Biol. Chem., Vol. 283, Issue 11, 99908, March 14, 2008
Collagen's "Disco" Domain
The two discoidin domain receptors (DDR1 and DDR2) are unique members of the receptor tyrosine kinase family in that they are activated by collagen and not small diffusible proteins. Thus, in addition to regulating fundamental cellular processes, DDRs control the remodeling of the extracellular matrix. In this Paper of the Week, Antonios D. Konitsiotis and colleagues define for the first time collagen binding sequence motifs that recognize DDR2. Their comprehensive analysis of collagen II revealed three high affinity binding sites, each of which contains a GFO triplet (O is hydroxyproline). The motif that bound with highest affinity was also conserved on collagens I and III and interestingly overlapped with collagen III binding site for von Willebrand factor. Using truncated peptides and alanine substitutions, Konitsiotis and colleagues found that the minimal binding sequence for this motif was GVMGFO, with the critical M and F residues properly positioned in close proximity in the triple helical collagen structure. These peptides were sufficient to activate DDR2 signaling, indicating that DDR2 activation does not require the presence of higher order fibrillar collagen.
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Molecular structures of the DDR2 collagen-binding DS domain and corresponding collagen II binding site.
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FOOTNOTES
See referenced article, J. Biol. Chem. 2008, 283, 6861-6868 
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Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.
