Fig. 1

Collagen structure and ligand binding. (A) Collagen in its native triple helical conformation contains both exposed and hidden ligand binding sites. Binding pockets for chaperone proteins (e.g., Hsp), DDRs, and lysyl oxidase enzymes are present on the triple helical surface. Similarly, surface binding sites bind to sequester LAIR-1. APP binding sites are present on the surface of collagen I. Binding pockets for MMPs and integrins are not exposed to prevent excessive collagen breakdown or downstream signaling. (B) With disease or age, the activity of MMPs is elevated leading to increased collagen degradation. Breakdown of collagen exposes additional binding sites (whose exact locations are largely unknown), including RGD domains for a sub-group of integrins. LAIR-1 binding decreases in disease leading to increased immune cell activation. Based on evidence of complement C3 and C4 binding to collagen in disease, we propose the actual binding sites become available following collagen damage, though this is yet to be determined