Year-end Sale % OFF 
Abstract
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 α10β1, 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 α10β1 and the positively-charged GROGER. Replacement of R215 with glutamine restored binding. Substituting arginine at the equivalent locus (Q214) in integrins α1 and α2 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 α10β1. 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 α10β1 is the main collagen-binding integrin.
Highlights
The collagen-binding integrin family is complete, with four established members, α1β1, α2β1, α10β1 and α11β1
GLOGEN occurs in III-7, a peptide that supports better adhesion of α10 I-domain than GFOGER, whilst III-4, which contains the relatively good α2β1-binding motif, GROGER [8,10], supported slight or negligible binding
Data obtained in the presence of EDTA are not shown for clarity. α10 I domain bound in Mg 2 + -dependent
Summary
The collagen-binding integrin family is complete, with four established members, α1β1, α2β1, α10β1 and α11β1. These are highly-conserved, heterodimeric receptors with an important structural feature in common, the presence of an I (inserted) domain which contains the metal ion-dependent adhesion site (MIDAS). 200-residue domain that, in the resting, non-ligated state, can co-ordinate a Mg 2 + ion. The octahedral co-ordination shell surrounding the metal ion is perturbed and reorganised by an incoming ligand, a negatively-charged glutamate residue that is crucial to the tight ligation of the receptor [1]. Several extracellular matrix (ECM) molecules are established as ligands for this group of integrins, including collagens, laminin, thrombospondin and others [2,3]. The family has been reviewed in depth recently [6], and needs little detailed introduction here
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
