Abstract
The hyaluronan receptor CD44 mediates cell adhesion/migration through tissue matrix during embryonic morphogenesis, tissue repair and leukocyte homing. However, despite their fundamental importance, the precise molecular details of CD44:hyaluronan interactions remain unknown. Here we have determined the crystal structure of the hyaluronan-binding domain complexed with a hyaluronan octasaccharide. This identifies the binding surface as a shallow groove in the main link module lined by a cluster of predominantly hydrophobic residues (tyrosine, alanine and isoleucine) and two key arginines, that together co-ordinate four sugars (GlcUA5-GlcNAc8) of the bound octasaccharide via hydrogen bonds rather than aromatic sugar stacking or ionic interactions. Moreover, we show that the complex experiences a conformational shift within the binding groove that brings an essential arginine residue (Arg45) into contact with ligand. A number of other residues within the link extension previously implicated in ligand-binding, make no apparent contacts with ligand. These data define a molecular interaction of fundamental importance to cell migration as well as providing the basis necessary for rational design of small molecule inhibitors for the treatment of inflammatory disease.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: 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.