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5fb8

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Revision as of 05:08, 9 September 2016

Structure of Interleukin-16 bound to the 14.1 antibody

Structural highlights

5fb8 is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1i16
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IL16_HUMAN] Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. Primes CD4+ T-cells for IL-2 and IL-15 responsiveness. Also induces T-lymphocyte expression of interleukin 2 receptor. Ligand for CD4.^[1] ^[2] Isoform 1 may act as a scaffolding protein that anchors ion channels in the membrane.^[3] ^[4] Isoform 3 is involved in cell cycle progression in T-cells. Appears to be involved in transcriptional regulation of SKP2 and is probably part of a transcriptional repression complex on the core promoter of the SKP2 gene. May act as a scaffold for GABPB1 (the DNA-binding subunit the GABP transcription factor complex) and HDAC3 thus maintaining transcriptional repression and blocking cell cycle progression in resting T-cells.^[5] ^[6]

Publication Abstract from PubMed

Interleukin-16 (IL-16) is reported to be a chemoattractant cytokine and modulator of T-cell activation, and has been identified as a ligand for CD4. The secreted active form of IL-16 has been detected at sites of TH1-mediated inflammation, such as those seen in autoimmune diseases, ischemic reperfusion injury (IRI) and tissue transplant rejection. Neutralisation of IL-16 recruitment to CD4, using an anti-IL16 antibody, has been shown to significantly attenuate inflammation and disease pathology in IRI, as well as in some autoimmune diseases. The 14.1 antibody is a monoclonal anti-IL-16 antibody, which when incubated with CD4+ cells is reported to cause a reduction in the TH1-type inflammatory response. Secreted IL-16 contains a characteristic PDZ-domain. PDZ domains are typically characterised by a defined globular structure, along with a peptide-binding site located in a groove between the alphaB and betaB structural elements and a highly conserved carboxylate-binding loop. The structure of the 14.1Fab fragment in complex with IL-16 has been solved by X-ray crystallography, revealing that binding of the antibody requires a conformational change in the IL-16 PDZ-domain. Our study reveals an unexpected mechanism of action for the mAb and identifies new opportunities for the further development of IL-16 targeted therapeutic drugs, including small molecules that mimic the interaction of the antibody.

Structure of a potential therapeutic antibody bound to IL-16: mechanistic insights and new therapeutic opportunities.,Hall G, Cullen E, Sawmynaden K, Arnold J, Fox S, Cowan R, Muskett FW, Matthews D, Merritt A, Kettleborough C, Cruikshank W, Taylor D, Bayliss R, Carr MD J Biol Chem. 2016 May 26. pii: jbc.M115.709303. PMID:27231345^[7]

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

References

↑ Center DM, Cruikshank WW, Zhang Y. Nuclear pro-IL-16 regulation of T cell proliferation: p27(KIP1)-dependent G0/G1 arrest mediated by inhibition of Skp2 transcription. J Immunol. 2004 Feb 1;172(3):1654-60. PMID:14734747
↑ Zhang Y, Tuzova M, Xiao ZX, Cruikshank WW, Center DM. Pro-IL-16 recruits histone deacetylase 3 to the Skp2 core promoter through interaction with transcription factor GABP. J Immunol. 2008 Jan 1;180(1):402-8. PMID:18097041
↑ Center DM, Cruikshank WW, Zhang Y. Nuclear pro-IL-16 regulation of T cell proliferation: p27(KIP1)-dependent G0/G1 arrest mediated by inhibition of Skp2 transcription. J Immunol. 2004 Feb 1;172(3):1654-60. PMID:14734747
↑ Zhang Y, Tuzova M, Xiao ZX, Cruikshank WW, Center DM. Pro-IL-16 recruits histone deacetylase 3 to the Skp2 core promoter through interaction with transcription factor GABP. J Immunol. 2008 Jan 1;180(1):402-8. PMID:18097041
↑ Center DM, Cruikshank WW, Zhang Y. Nuclear pro-IL-16 regulation of T cell proliferation: p27(KIP1)-dependent G0/G1 arrest mediated by inhibition of Skp2 transcription. J Immunol. 2004 Feb 1;172(3):1654-60. PMID:14734747
↑ Zhang Y, Tuzova M, Xiao ZX, Cruikshank WW, Center DM. Pro-IL-16 recruits histone deacetylase 3 to the Skp2 core promoter through interaction with transcription factor GABP. J Immunol. 2008 Jan 1;180(1):402-8. PMID:18097041
↑ Hall G, Cullen E, Sawmynaden K, Arnold J, Fox S, Cowan R, Muskett FW, Matthews D, Merritt A, Kettleborough C, Cruikshank W, Taylor D, Bayliss R, Carr MD. Structure of a potential therapeutic antibody bound to IL-16: mechanistic insights and new therapeutic opportunities. J Biol Chem. 2016 May 26. pii: jbc.M115.709303. PMID:27231345 doi:http://dx.doi.org/10.1074/jbc.M115.709303

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/5fb8"

@@ Line 6: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1i16|1i16]]</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=5fb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fb8 OCA], [http://pdbe.org/5fb8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fb8 RCSB], [http://www.ebi.ac.uk/pdbsum/5fb8 PDBsum]</span></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=5fb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fb8 OCA], [http://pdbe.org/5fb8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fb8 RCSB], [http://www.ebi.ac.uk/pdbsum/5fb8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fb8 ProSAT]</span></td></tr>
 </table>
 == Function ==

5fb8

From Proteopedia

Revision as of 05:08, 9 September 2016

Structure of Interleukin-16 bound to the 14.1 antibody

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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