Title : Structures of
CD200 /
CD200 receptor family and implications for topology, regulation, and evolution
Abstract :
- CD200 is a widely distributed membrane glycoprotein that regulates myeloid cell activity through its interaction with an inhibitory receptor ( CD200R )
- The interaction is of interest as a target for treating excessive inflammation and for treating leukemia
- There are closely related proteins to CD200R that give activating signals making this a "paired receptor .
- We report X-ray crystallography structures for the inhibitory CD200R , the activating receptor CD200RLa , and a complex between CD200R and CD200
- Both CD200 and CD200R contain two Ig-like domains and interact through their NHâ‚‚ terminal domains compatible with immunological synapse-like interactions occurring between myeloid cells and other CD200-expressing cells
- The failure of the activating receptor to bind CD200 resides in subtle changes around the interface
- CD200 has been acquired by herpes viruses to mimic the host interaction
- CD200R has evolved rapidly presumably driven by pathogen pressure but it may also be important in homeostasis through interactions with commensal bacteria