Integrins are a large family of α and β heterodimeric receptors that mediate cell–cell and cell–extracellular matrix (ECM) interactions.
7 It was previously confirmed that integrin α2 and β1 subunits may be the target of collagen cell binding. The integrin α2 subunit contains an additional I domain inserted into the head region, which plays a central role in collagen binding, so the potential role of the integrin α2-I domain–collagen binding complex was studied to explore the regulatory mechanism and specific interference site of opticin in this study.
7 A specific motif recognized by the integrin α2-I domain has been identified as GXXGER in collagen, and the sequence GFOGER (where O is hydroxyproline) is the minimal recognition motif of GXXGER.
8 Structural studies reveal that the integrin α2-I domain has two alternative conformations: open and closed. Activation of the integrin α2-I domain–GXXGER complex requires a conserved metal binding site known as the metal ion–dependent adhesion site (MIDAS) motif in the integrin α2-I domain which may be occupied by metal ions.
9–12 The interaction of metal ions and MIDAS exposes the α7 helix at the C-terminal of the integrin α2-I domain, which opens up the collagen binding site and allows further binding to glutamic acid residues in the collagen sequence GXXGER.
13,14 Mg
2+ functions as a switch of the integrin α2-I domain–collagen binding complex and triggers conformational changes in the integrin α2-I domain from the closed, unliganded to the open, liganded state. As mentioned above, the interaction of Mg
2+ and MIDAS exposes the α7 helix at the C-terminal of the integrin α2-I domain, which opens up the collagen binding site and allows further binding to glutamic acid residues in the collagen sequence GXXGER. Thus, it has been hypothesized that opticin may regulate binding of the integrin α2-I domain to collagen by interfering with Mg
2+, which will further interfere with the collagen-stimulating angiogenesis. Because RhoA/ROCK1 is activated by integrin signals, a conduit for the transmission of signals into cells is provided.
15 This study was conducted to investigate the role of
OPTC in the formation of the integrin α2-I domain–GXXGER complex and the signal activities of RhoA/ROCK1.