4cmm

From Proteopedia

(Difference between revisions)

Current revision

Structure of human CD47 in complex with human Signal Regulatory Protein (SIRP) alpha v1

Structural highlights

4cmm is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.92Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SHPS1_HUMAN Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.^[1] ^[2]

Publication Abstract from PubMed

CD47 is a widely distributed membrane protein that interacts with Signal-regulatory protein alpha (SIRPalpha), an inhibitory receptor on myeloid cells that gives a do-not-eat-me signal. Manipulation of the interaction is of considerable interest in the immunotherapy of cancer and in xenotransplantation. The amino terminal ligand binding domain of SIRPalpha is highly polymorphic in contrast to the single Ig-like domain of CD47. There is confusion as to whether the polymorphisms will affect ligand binding but this is an important point for this interaction and other paired receptors being considered for as targets for therapy. We show by X-ray crystallography that one human SIRPalpha allele differing in 13 amino acid residues has a very similar binding site and that several different alleles all bind CD47 with similar affinity as expected as the residues are mostly surface exposed and distant from the binding site. A peptide from the binding site of CD47 has been reported to mimic the CD47 interaction with SIRPalpha but we could find no binding. We discuss the possible pitfalls in determining the affinity of weak interactions and also speculate on how SIRPalpha polymorphisms may have been selected by pathogens and how this may also be true in other paired receptors such as the KIRs.

Polymorphisms in the human inhibitory signal-regulatory protein alpha do not affect binding to its ligand CD47.,Hatherley D, Lea SM, Johnson S, Barclay AN J Biol Chem. 2014 Feb 19. PMID:24550402^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Timms JF, Swanson KD, Marie-Cardine A, Raab M, Rudd CE, Schraven B, Neel BG. SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages. Curr Biol. 1999 Aug 26;9(16):927-30. PMID:10469599
↑ Latour S, Tanaka H, Demeure C, Mateo V, Rubio M, Brown EJ, Maliszewski C, Lindberg FP, Oldenborg A, Ullrich A, Delespesse G, Sarfati M. Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation. J Immunol. 2001 Sep 1;167(5):2547-54. PMID:11509594
↑ Hatherley D, Lea SM, Johnson S, Barclay AN. Polymorphisms in the human inhibitory signal-regulatory protein alpha do not affect binding to its ligand CD47. J Biol Chem. 2014 Feb 19. PMID:24550402 doi:http://dx.doi.org/10.1074/jbc.M114.550558

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cmm"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4cmm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CMM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CMM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.92&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4cmm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cmm OCA], [https://pdbe.org/4cmm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cmm RCSB], [https://www.ebi.ac.uk/pdbsum/4cmm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cmm ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/SHPS1_HUMAN SHPS1_HUMAN]] Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.<ref>PMID:10469599</ref> <ref>PMID:11509594</ref>
+[https://www.uniprot.org/uniprot/SHPS1_HUMAN SHPS1_HUMAN] Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.<ref>PMID:10469599</ref> <ref>PMID:11509594</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4cmm

From Proteopedia

Current revision

Structure of human CD47 in complex with human Signal Regulatory Protein (SIRP) alpha v1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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