Title : Structures of
CD6 and Its Ligand
CD166 Give Insight into Their Interaction
Abstract :
- CD6 is a transmembrane protein with an extracellular region containing three scavenger receptor cysteine rich (SRCR) domains
- The membrane proximal domain of CD6 binds the N-terminal immunoglobulin superfamily (IgSF) domain of another cell surface receptor , CD166 , which also engages in homophilic interactions
- CD6 expression is mainly restricted to T cells, and the interaction between CD6 and CD166 regulates T-cell activation
- We have solved the X-ray crystal structures of the three SRCR domains of CD6 and two N-terminal domains of CD166
- This first structure of consecutive SRCR domains reveals a nonlinear organization
- We characterized the binding sites on CD6 and CD166 and showed that a SNP in CD6 causes glycosylation that hinders the CD6 / CD166 interaction
- Native mass spectrometry analysis showed that there is competition between the heterophilic and homophilic interactions
- These data give insight into how interactions of consecutive SRCR domains are perturbed by SNPs and potential therapeutic reagents