5tzt

From Proteopedia

(Difference between revisions)

Revision as of 10:19, 22 November 2017

Crystal structure of human CD47 ECD bound to Fab of C47B161

Structural highlights

5tzt is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	5tz2, 5tzu
Gene:	CD47, MER6 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CD47_HUMAN] Has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. Plays an important role in memory formation and synaptic plasticity in the hippocampus (By similarity). Receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation. May play a role in membrane transport and/or integrin dependent signal transduction. May prevent premature elimination of red blood cells. May be involved in membrane permeability changes induced following virus infection.^[1] ^[2] ^[3]

Publication Abstract from PubMed

CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPalpha. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPalpha blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2sigma C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices.

Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies.,Pietsch EC, Dong J, Cardoso R, Zhang X, Chin D, Hawkins R, Dinh T, Zhou M, Strake B, Feng PH, Rocca M, Santos CD, Shan X, Danet-Desnoyers G, Shi F, Kaiser E, Millar HJ, Fenton S, Swanson R, Nemeth JA, Attar RM Blood Cancer J. 2017 Feb 24;7(2):e536. doi: 10.1038/bcj.2017.7. PMID:28234345^[4]

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

References

↑ Lindberg FP, Gresham HD, Schwarz E, Brown EJ. Molecular cloning of integrin-associated protein: an immunoglobulin family member with multiple membrane-spanning domains implicated in alpha v beta 3-dependent ligand binding. J Cell Biol. 1993 Oct;123(2):485-96. PMID:7691831
↑ 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
↑ Piccio L, Vermi W, Boles KS, Fuchs A, Strader CA, Facchetti F, Cella M, Colonna M. Adhesion of human T cells to antigen-presenting cells through SIRPbeta2-CD47 interaction costimulates T-cell proliferation. Blood. 2005 Mar 15;105(6):2421-7. Epub 2004 Sep 21. PMID:15383453 doi:10.1182/blood-2004-07-2823
↑ Pietsch EC, Dong J, Cardoso R, Zhang X, Chin D, Hawkins R, Dinh T, Zhou M, Strake B, Feng PH, Rocca M, Santos CD, Shan X, Danet-Desnoyers G, Shi F, Kaiser E, Millar HJ, Fenton S, Swanson R, Nemeth JA, Attar RM. Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies. Blood Cancer J. 2017 Feb 24;7(2):e536. doi: 10.1038/bcj.2017.7. PMID:28234345 doi:http://dx.doi.org/10.1038/bcj.2017.7

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5tzt"

Categories: Human | Cardoso, R M.F | Antigen-fab complex | Immune system | Immunoglobulin

@@ Line 3: / Line 3: @@
 <StructureSection load='5tzt' size='340' side='right' caption='[[5tzt]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5tzt]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TZT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TZT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5tzt]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TZT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TZT FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tz2|5tz2]], [[5tzu|5tzu]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD47, MER6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tzt OCA], [http://pdbe.org/5tzt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tzt RCSB], [http://www.ebi.ac.uk/pdbsum/5tzt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tzt ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Cardoso, R M.F]]
 [[Category: Antigen-fab complex]]
 [[Category: Immune system]]
 [[Category: Immunoglobulin]]

5tzt

From Proteopedia

Revision as of 10:19, 22 November 2017

Crystal structure of human CD47 ECD bound to Fab of C47B161

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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