A structural prospective for collagen receptors such as DDR and their binding of the collagen fibril

• Published in: Biochimica et biophysica acta. Molecular cell research 2019-11, Vol.1866 (11), p.118478-118478, Article 118478
• Main Authors: Orgel, Joseph P.R.O., Madhurapantula, Rama S.
• Format: Article
• Language: English
• Subjects: Animals; Cell Adhesion - physiology; Cell Movement - physiology; Cell Proliferation - physiology; Collagen; Collagen - chemistry; Collagen - metabolism; DDR; Discoidin Domain Receptor 1; Discoidin Domain Receptor 2; Discoidin Domain Receptors - chemistry; Discoidin Domain Receptors - metabolism; Fibril; Fibrillar Collagens - chemistry; Fibrillar Collagens - metabolism; Humans; Ligands; Models, Molecular; Molecular Structure; Neoplasms - metabolism; Proliferation; Protein Binding; Protein Interaction Domains and Motifs; Receptor; Receptor Protein-Tyrosine Kinases; Receptors, Collagen - chemistry; Receptors, Collagen - metabolism; Signal Transduction; Structure
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2019.04.008

The structure of the collagen fibril surface directly effects and possibly assists the management of collagen receptor interactions. An important class of collagen receptors, the receptor tyrosine kinases of the Discoidin Domain Receptor family (DDR1 and DDR2), are differentially activated by specific collagen types and play important roles in cell adhesion, migration, proliferation, and matrix remodeling. This review discusses their structure and function as it pertains directly to the fibrillar collagen structure with which they interact far more readily than they do with isolated molecular collagen. This prospective provides further insight into the mechanisms of activation and rational cellular control of this important class of receptors while also providing a comparison of DDR-collagen interactions with other receptors such as integrin and GPVI. When improperly regulated, DDR activation can lead to abnormal cellular proliferation activities such as in cancer. Hence how and when the DDRs associate with the major basis of mammalian tissue infrastructure, fibrillar collagen, should be of keen interest. •Collagen receptors as they interact with their substrate, the collagen fibril•Collagen fibril is a complex, organized, ordered structure.•Collagen fibril surface has differential receptor accessibility.•DDR has two fibril receptor sites, both at least partly obscured.•Damage to fibril, remodeling and or mechanical adjustments appear needed for binding.