Title : Paired
receptor specificity explained by structures of signal regulatory
proteins alone and complexed with
CD47
Abstract :
- CD47 is a widely distributed cell-surface protein that acts a marker of self through interactions of myeloid and neural cells
- We describe the high-resolution X-ray crystallographic structures of the immunoglobulin superfamily domain of CD47 alone and in complex with the N-terminal ligand-binding domain of signal regulatory protein alpha ( SIRPalpha )
- The unusual and convoluted interacting face of CD47 , comprising the N terminus and loops at the end of the domain, intercalates with the corresponding regions in SIRPalpha
- We have also determined structures of the N-terminal domains of SIRPbeta, SIRPbeta(2), and SIRPgamma ; proteins that are closely related to SIRPalpha but bind CD47 with negligible or reduced affinity
- These results explain the specificity of CD47 for the SIRP family of paired receptors in atomic detail
- Analysis of SIRPalpha polymorphisms suggests that these, as well as the activating SIRPs, may have evolved to counteract pathogen binding to the inhibitory SIRPalpha receptor
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 2. CD47, domain
- 2. signal regulatory protein alpha, domain
- 3. CD47, face
- 3. SIRPalpha, regions
- 4. SIRPgamma, domains
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):