Unique charge-dependent constraint on collagen recognition by integrin α10β1

The collagen-binding integrins recognise collagen through their inserted (I) domain, where co-ordination of a Mg2+ ion in the metal ion-dependent site is reorganised by ligation by a collagen glutamate residue found in specific collagen hexapeptide motifs. Here we show that GROGER, found in the N-terminal domain of collagens I and III, is only weakly recognised by alpha 10 beta 1, an important collagen receptor on chondrocytes, contrasting with the other collagen-binding integrins. Alignment of I domain sequence and molecular modelling revealed a clash between a unique arginine residue (R215) in al alpha 10 beta 1 and the positively-charged GROGER. Replacement of R215 with glutamine restored binding. Substituting arginine at the equivalent locus (Q214) in integrins alpha 1 and alpha 2 I domains impaired their binding to GROGER. Collagen II, abundant in cartilage, lacks GROGER. GRSGET is uniquely expressed in the C-terminus of collagen II, but this motif is similarly not recognised by al Opt These data suggest an evolutionary imperative to maintain accessibility of the terminal domains of collagen II in tissues such as cartilage, perhaps during endochondral ossification, where alpha 10 beta 1 is the main collagen-binding integrin. (C) 2017 Published by Elsevier B.V.