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@article{An:2015:10.1074/jbc.M115.674507,
author = {An, B and Abbonante, V and Xu, H and Gavriilidou, D and Yoshizumi, A and Bihan, D and Farndale, RW and Kaplan, D and Balduini, A and Leitinger, B and Brodsky, B},
doi = {10.1074/jbc.M115.674507},
journal = {Journal of Biological Chemistry},
pages = {4343--4355},
title = {Recombinant Collagen Engineered to Bind to Discoidin Domain Receptors Functions as a Receptor Inhibitor},
url = {http://dx.doi.org/10.1074/jbc.M115.674507},
volume = {291},
year = {2015}
}

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TY  - JOUR
AB  - A bacterial collagen-like protein Scl2 has been developed as a recombinant collagen model system to host human collagen ligand binding sequences, with the goal of generating biomaterials with selective collagen bioactivities. Defined binding sites in human collagen for integrins, fibronectin, heparin, and MMP-1 have been introduced into the triple-helical domain of the bacterial collagen and led to the expected biological activities. The modular insertion of activities is extended here to the discoidin domain receptors (DDRs), which are collagen activated receptor tyrosine kinases. Insertion of the DDR binding sequence from human collagen III into bacterial collagen led to specific receptor binding. However, even at the highest testable concentrations, the construct was unable to stimulate DDR autophosphorylation. The recombinant collagen expressed in E. coli does not contain hydroxyproline (Hyp), and complementary synthetic peptide studies showed that replacement of Hyp by Pro at the critical Gly-Val-Met-Gly-Phe-Hyp position decreased the DDR binding affinity and consequently required a higher concentration for the induction of receptor activation. The ability of the recombinant bacterial collagen to bind the DDRs without inducing kinase activation suggested it could interfere with the interactions between animal collagen and the DDRs, and such an inhibitory role was confirmed in vitro and with a cell migration assay. This study illustrates that recombinant collagen can complement synthetic peptides in investigating structure-activity relationships, and this system has the potential for the introduction or inhibition of specific biological activities.
AU  - An,B
AU  - Abbonante,V
AU  - Xu,H
AU  - Gavriilidou,D
AU  - Yoshizumi,A
AU  - Bihan,D
AU  - Farndale,RW
AU  - Kaplan,D
AU  - Balduini,A
AU  - Leitinger,B
AU  - Brodsky,B
DO  - 10.1074/jbc.M115.674507
EP  - 4355
PY  - 2015///
SN  - 1083-351X
SP  - 4343
TI  - Recombinant Collagen Engineered to Bind to Discoidin Domain Receptors Functions as a Receptor Inhibitor
T2  - Journal of Biological Chemistry
UR  - http://dx.doi.org/10.1074/jbc.M115.674507
UR  - http://hdl.handle.net/10044/1/28693
VL  - 291
ER  -

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