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Recombinant Collagen Engineered to Bind to Discoidin Domain Receptor Functions as a Receptor Inhibitor
An, Bo1; Abbonante, Vittorio2; Xu, Huifang3,6; Gavriilidou, Despoina3; Yoshizumi, Ayumi4; Bihan, Dominique5; Farndale, Richard W.5; Kaplan, David L.1; Balduini, Alessandra1,2; Leitinger, Birgit3; Brodsky, Barbara1
2016-02-26
发表期刊JOURNAL OF BIOLOGICAL CHEMISTRY
卷号291期号:9页码:4343-4355
摘要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 Escherichia 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.
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine
DOI10.1074/jbc.M115.674507
关键词[WOS]STREPTOCOCCUS-PYOGENES ; TYROSINE KINASES ; TRIPLE-HELICES ; PROTEIN ; IDENTIFICATION ; DDR2 ; PEPTIDES ; SITES ; STABILITY ; CLEAVAGE
收录类别SCI
语种英语
WOS研究方向Biochemistry & Molecular Biology
项目资助者National Institutes of Health(EB011620 ; Medical Research Council United Kingdom(G0701121) ; Biotechnology and Biological Sciences Research Council United Kingdom(BB/I011226/1) ; Biomedical Resource Grant from Wellcome Trust(094470/Z/10/Z) ; CARIPLO13-ICH (Cariplo Foundation)(2013.0717) ; GM60048)
WOS类目Biochemistry & Molecular Biology
WOS记录号WOS:000371604600008
引用统计
文献类型期刊论文
条目标识符http://ir.qibebt.ac.cn/handle/337004/8060
专题酶工程研究组
作者单位1.Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA
2.Univ Pavia, Ist Ric & Cura Carattere Sci San Matteo Fdn, Dept Mol Med, I-27100 Pavia, Italy
3.Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Mol Med Sect, Sir Alexander Fleming Bldg, London SW7 2AZ, England
4.Toho Univ, Sch Med, Fac Med, Dept Microbiol & Infect Dis, Tokyo 1438540, Japan
5.Univ Cambridge, Dept Biochem, Tennis Court Rd, Cambridge CB2 1QW, England
6.Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Key Lab Biofuels, Qingdao, Peoples R China
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GB/T 7714
An, Bo,Abbonante, Vittorio,Xu, Huifang,et al. Recombinant Collagen Engineered to Bind to Discoidin Domain Receptor Functions as a Receptor Inhibitor[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2016,291(9):4343-4355.
APA An, Bo.,Abbonante, Vittorio.,Xu, Huifang.,Gavriilidou, Despoina.,Yoshizumi, Ayumi.,...&Brodsky, Barbara.(2016).Recombinant Collagen Engineered to Bind to Discoidin Domain Receptor Functions as a Receptor Inhibitor.JOURNAL OF BIOLOGICAL CHEMISTRY,291(9),4343-4355.
MLA An, Bo,et al."Recombinant Collagen Engineered to Bind to Discoidin Domain Receptor Functions as a Receptor Inhibitor".JOURNAL OF BIOLOGICAL CHEMISTRY 291.9(2016):4343-4355.
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