2box

EGF Domains 1,2,5 of human EMR2, a 7-TM immune system molecule, in complex with strontium.EGF Domains 1,2,5 of human EMR2, a 7-TM immune system molecule, in complex with strontium.

Structural highlights

2box is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2bo2, 2bou
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[EMR2_HUMAN] Cell surface receptor that binds to the chondroitin sulfate moiety of glycosaminoglycan chains and promotes cell attachment. Promotes granulocyte chemotaxis, degranulation and adhesion. In macrophages, promotes the release of inflammatory cytokines, including IL8 and TNF.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

CD97, the archetypal member of the EGF-TM7 protein family, is constitutively expressed on granulocytes and monocytes and rapidly up-regulated on T and B cells following activation. The key isoform of CD97 expressed on leukocytes binds the complement regulatory protein CD55 (also termed decay-accelerating factor). CD97 has been shown recently to mediate co-stimulation of T cells via CD55. Here, we demonstrate that blocking the interaction between CD55 on monocytes and CD97 on T cells leads to inhibition of proliferation and interferon-gamma secretion. This implies that bidirectional interactions between CD97 and CD55 are involved in T cell regulation. Structural studies presented here reveal the molecular basis for this activity. We have solved the structure of EMR2, a very close homolog of CD97, using x-ray crystallography. NMR-based chemical shift mapping of the EMR2-CD55 interaction has allowed us to generate a model for the CD97-CD55 complex. The structure of the complex reveals that the T cell and complement regulatory activities of CD55 occur on opposite faces of the molecule. This suggests that CD55 might simultaneously regulate both the innate and adaptive immune responses, and we have shown that CD55 can still regulate complement when bound to CD97.

Structural and functional characterization of a novel T cell receptor co-regulatory protein complex, CD97-CD55.,Abbott RJ, Spendlove I, Roversi P, Fitzgibbon H, Knott V, Teriete P, McDonnell JM, Handford PA, Lea SM J Biol Chem. 2007 Jul 27;282(30):22023-32. Epub 2007 Apr 20. PMID:17449467^[4]

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

References

↑ Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH. The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood. 2003 Oct 15;102(8):2916-24. Epub 2003 Jun 26. PMID:12829604 doi:10.1182/blood-2002-11-3540
↑ Yona S, Lin HH, Dri P, Davies JQ, Hayhoe RP, Lewis SM, Heinsbroek SE, Brown KA, Perretti M, Hamann J, Treacher DF, Gordon S, Stacey M. Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function. FASEB J. 2008 Mar;22(3):741-51. Epub 2007 Oct 10. PMID:17928360 doi:10.1096/fj.07-9435com
↑ Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP, Yona S, Stacey M, Gordon S, Chang GW, Lin HH. Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol Cell Biol. 2012 Apr;32(8):1408-20. doi: 10.1128/MCB.06557-11. Epub 2012 Feb, 6. PMID:22310662 doi:10.1128/MCB.06557-11
↑ Abbott RJ, Spendlove I, Roversi P, Fitzgibbon H, Knott V, Teriete P, McDonnell JM, Handford PA, Lea SM. Structural and functional characterization of a novel T cell receptor co-regulatory protein complex, CD97-CD55. J Biol Chem. 2007 Jul 27;282(30):22023-32. Epub 2007 Apr 20. PMID:17449467 doi:M702588200

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OCA

[1] Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH. The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood. 2003 Oct 15;102(8):2916-24. Epub 2003 Jun 26. PMID:12829604 doi:10.1182/blood-2002-11-3540

[2] Yona S, Lin HH, Dri P, Davies JQ, Hayhoe RP, Lewis SM, Heinsbroek SE, Brown KA, Perretti M, Hamann J, Treacher DF, Gordon S, Stacey M. Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function. FASEB J. 2008 Mar;22(3):741-51. Epub 2007 Oct 10. PMID:17928360 doi:10.1096/fj.07-9435com

[3] Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP, Yona S, Stacey M, Gordon S, Chang GW, Lin HH. Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol Cell Biol. 2012 Apr;32(8):1408-20. doi: 10.1128/MCB.06557-11. Epub 2012 Feb, 6. PMID:22310662 doi:10.1128/MCB.06557-11

[4] Abbott RJ, Spendlove I, Roversi P, Fitzgibbon H, Knott V, Teriete P, McDonnell JM, Handford PA, Lea SM. Structural and functional characterization of a novel T cell receptor co-regulatory protein complex, CD97-CD55. J Biol Chem. 2007 Jul 27;282(30):22023-32. Epub 2007 Apr 20. PMID:17449467 doi:M702588200

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