5iwl

From Proteopedia

(Difference between revisions)

Revision as of 02:52, 13 July 2016

CD47-diabody complex

Structural highlights

5iwl is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
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

Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with limited treatment options. CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPalpha), which serves as an inhibitory receptor on macrophages. Here, we found that CD47 is highly expressed on the surface of human SCLC cells; therefore, we investigated CD47-blocking immunotherapies as a potential approach for SCLC treatment. Disruption of the interaction of CD47 with SIRPalpha using anti-CD47 antibodies induced macrophage-mediated phagocytosis of human SCLC patient cells in culture. In a murine model, administration of CD47-blocking antibodies or targeted inactivation of the Cd47 gene markedly inhibited SCLC tumor growth. Furthermore, using comprehensive antibody arrays, we identified several possible therapeutic targets on the surface of SCLC cells. Antibodies to these targets, including CD56/neural cell adhesion molecule (NCAM), promoted phagocytosis in human SCLC cell lines that was enhanced when combined with CD47-blocking therapies. In light of recent clinical trials for CD47-blocking therapies in cancer treatment, these findings identify disruption of the CD47/SIRPalpha axis as a potential immunotherapeutic strategy for SCLC. This approach could enable personalized immunotherapeutic regimens in patients with SCLC and other cancers.

CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer.,Weiskopf K, Jahchan NS, Schnorr PJ, Cristea S, Ring AM, Maute RL, Volkmer AK, Volkmer JP, Liu J, Lim JS, Yang D, Seitz G, Nguyen T, Wu D, Jude K, Guerston H, Barkal A, Trapani F, George J, Poirier JT, Gardner EE, Miles LA, de Stanchina E, Lofgren SM, Vogel H, Winslow MM, Dive C, Thomas RK, Rudin CM, van de Rijn M, Majeti R, Garcia KC, Weissman IL, Sage J J Clin Invest. 2016 Jul 1;126(7):2610-20. doi: 10.1172/JCI81603. Epub 2016 Jun, 13. PMID:27294525^[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
↑ Weiskopf K, Jahchan NS, Schnorr PJ, Cristea S, Ring AM, Maute RL, Volkmer AK, Volkmer JP, Liu J, Lim JS, Yang D, Seitz G, Nguyen T, Wu D, Jude K, Guerston H, Barkal A, Trapani F, George J, Poirier JT, Gardner EE, Miles LA, de Stanchina E, Lofgren SM, Vogel H, Winslow MM, Dive C, Thomas RK, Rudin CM, van de Rijn M, Majeti R, Garcia KC, Weissman IL, Sage J. CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer. J Clin Invest. 2016 Jul 1;126(7):2610-20. doi: 10.1172/JCI81603. Epub 2016 Jun, 13. PMID:27294525 doi:http://dx.doi.org/10.1172/JCI81603

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/5iwl"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5iwl is ON HOLD  until Paper Publication
+==CD47-diabody complex==
+<StructureSection load='5iwl' size='340' side='right' caption='[[5iwl]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5iwl]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IWL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IWL FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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='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=5iwl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iwl OCA], [http://pdbe.org/5iwl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iwl RCSB], [http://www.ebi.ac.uk/pdbsum/5iwl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iwl ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/CD47_HUMAN 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.<ref>PMID:7691831</ref> <ref>PMID:11509594</ref> <ref>PMID:15383453</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with limited treatment options. CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPalpha), which serves as an inhibitory receptor on macrophages. Here, we found that CD47 is highly expressed on the surface of human SCLC cells; therefore, we investigated CD47-blocking immunotherapies as a potential approach for SCLC treatment. Disruption of the interaction of CD47 with SIRPalpha using anti-CD47 antibodies induced macrophage-mediated phagocytosis of human SCLC patient cells in culture. In a murine model, administration of CD47-blocking antibodies or targeted inactivation of the Cd47 gene markedly inhibited SCLC tumor growth. Furthermore, using comprehensive antibody arrays, we identified several possible therapeutic targets on the surface of SCLC cells. Antibodies to these targets, including CD56/neural cell adhesion molecule (NCAM), promoted phagocytosis in human SCLC cell lines that was enhanced when combined with CD47-blocking therapies. In light of recent clinical trials for CD47-blocking therapies in cancer treatment, these findings identify disruption of the CD47/SIRPalpha axis as a potential immunotherapeutic strategy for SCLC. This approach could enable personalized immunotherapeutic regimens in patients with SCLC and other cancers.
-Authors:
+CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer.,Weiskopf K, Jahchan NS, Schnorr PJ, Cristea S, Ring AM, Maute RL, Volkmer AK, Volkmer JP, Liu J, Lim JS, Yang D, Seitz G, Nguyen T, Wu D, Jude K, Guerston H, Barkal A, Trapani F, George J, Poirier JT, Gardner EE, Miles LA, de Stanchina E, Lofgren SM, Vogel H, Winslow MM, Dive C, Thomas RK, Rudin CM, van de Rijn M, Majeti R, Garcia KC, Weissman IL, Sage J J Clin Invest. 2016 Jul 1;126(7):2610-20. doi: 10.1172/JCI81603. Epub 2016 Jun, 13. PMID:27294525<ref>PMID:27294525</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5iwl" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Di, W]]
+[[Category: Garcia, K C]]
+[[Category: Jude, K M]]
+[[Category: Cell adhesion]]
+[[Category: Complex]]
+[[Category: Diabody]]
+[[Category: Receptor]]

5iwl

From Proteopedia

Revision as of 02:52, 13 July 2016

CD47-diabody complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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