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Functional elements on SIRPalpha IgV domain mediate cell surface binding to CD47.
Yuan Liu1, Qiao Tong, Yubin Zhou
1Department of Biology, Georgia State University, Atlanta, GA 30302, USA. yliu@gsu.edu
Journal of Molecular Biology
|October 31, 2006
Summary
Signal regulatory protein alpha (SIRPalpha) binds CD47 via specific amino acid residues in its IgV domain, including Gln67 and Ala/Val57. These residues are crucial for SIRPalpha
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Signal regulatory protein (SIRP) alpha and beta1 are leukocyte isoforms with distinct functions.
- SIRPalpha binding to CD47 regulates leukocyte functions like adhesion and transmigration.
- SIRPbeta1 shares structural homology with SIRPalpha but does not bind CD47.
Purpose of the Study:
- To identify specific amino acid residues in SIRPalpha's IgV domain responsible for CD47 binding.
- To elucidate the molecular basis for differential CD47 interaction between SIRPalpha and SIRPbeta1.
Main Methods:
- Site-directed mutagenesis of SIRPalpha IgV domain residues.
- Biochemical assays to assess SIRPalpha-CD47 binding.
- Functional assays including cell adhesion and leukocyte transmigration.
Main Results:
- Key residues Gln67 and Ala/Val57 in SIRPalpha's IgV domain are critical for CD47 binding.
- Mutation of these residues abolishes SIRPalpha-CD47 interaction and associated cellular functions.
- Introducing these residues into SIRPbeta1 confers CD47-binding capability, confirming their essential role.
Conclusions:
- Specific amino acids (Gln67, Ala/Val57, Met102) dictate SIRPalpha's exclusive binding to CD47.
- This study reveals the molecular determinants of SIRPalpha-CD47 interaction.
- Findings provide insight into the structural basis for distinct SIRP isoform-mediated cellular responses.
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