3ux9: Difference between revisions
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[[ | ==Structural insights into a human anti-IFN antibody exerting therapeutic potential for systemic lupus erythematosus== | ||
<StructureSection load='3ux9' size='340' side='right' caption='[[3ux9]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ux9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UX9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UX9 FirstGlance]. <br> | |||
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IFNA1, IFNA13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3ux9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ux9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ux9 RCSB], [http://www.ebi.ac.uk/pdbsum/3ux9 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Increasing evidences suggest that the type I interferon alpha (IFNalpha) plays a critical role in the etiopathogenesis of systemic lupus erythematosus (SLE), which makes it a promising therapeutic target for the treatment of the disease. By screening a large size non-immune human antibody library, we have developed a human single-chain antibody (ScFv) AIFNalpha1bScFv01 and corresponding whole antibody AIFNalpha1bIgG01 to human interferon alpha1b (IFNalpha1b) with high specificity and high affinity. The IgG antibody could down-regulate the expression of ISG15 and IFIT-1 induced by either recombinant IFNalpha1b or naive IFNalpha from SLE patients' sera, and reduced total serum IgG and IgM antibodies level in a pristane-primed lupus-like mouse model. The crystal structure of AIFNalpha1bScFv01-IFNalpha1b complex solved to 2.8 A resolution revealed that both Pro26-Gln40 region in loop AB and Glu147-Arg150 region in helix E of IFNalpha1b contribute to binding with AIFNalpha1bScFv01. Four residues of above two regions (Leu30, Asp32, Asp35 and Arg150) are critical for the formation of antigen-antibody complexes. AIFNalpha1bScFv01 shares partial epitopes of IFNalpha1b with its receptor IFNAR2 but with much higher binding affinity to IFNalpha1b than IFNAR2. Thus, AIFNalpha1bIgG01 exhibits its neutralizing activity through competition with IFNAR2 to bind with IFNalpha and prevents the activation of IFNalpha-mediated signaling pathway. Our results highlight the potential use of the human antibody for modulating the activity of IFNalpha in SLE. | |||
Structural insights into a human anti-IFN antibody exerting therapeutic potential for systemic lupus erythematosus.,Ouyang S, Gong B, Li JZ, Zhao LX, Wu W, Zhang FS, Sun L, Wang SJ, Pan M, Li C, Liang W, Shaw N, Zheng J, Zhao GP, Wang Y, Liu ZJ, Liang M J Mol Med (Berl). 2012 Feb 4. PMID:22307521<ref>PMID:22307521</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[Monoclonal Antibody|Monoclonal Antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[ | |||
== | |||
< | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Liang, M F | [[Category: Liang, M F]] | ||
[[Category: Liang, W | [[Category: Liang, W]] | ||
[[Category: Liu, Z J | [[Category: Liu, Z J]] | ||
[[Category: Ouyang, S | [[Category: Ouyang, S]] | ||
[[Category: Shaw, N | [[Category: Shaw, N]] | ||
[[Category: Zhao, L X | [[Category: Zhao, L X]] | ||
[[Category: Cytokine-immune system complex]] | [[Category: Cytokine-immune system complex]] | ||
[[Category: Five helice]] | [[Category: Five helice]] | ||
[[Category: Hydrophobic interaction]] | [[Category: Hydrophobic interaction]] | ||
[[Category: Long loop connecting helix]] | [[Category: Long loop connecting helix]] | ||
Revision as of 12:57, 4 January 2015
Structural insights into a human anti-IFN antibody exerting therapeutic potential for systemic lupus erythematosusStructural insights into a human anti-IFN antibody exerting therapeutic potential for systemic lupus erythematosus
Structural highlights
Publication Abstract from PubMedIncreasing evidences suggest that the type I interferon alpha (IFNalpha) plays a critical role in the etiopathogenesis of systemic lupus erythematosus (SLE), which makes it a promising therapeutic target for the treatment of the disease. By screening a large size non-immune human antibody library, we have developed a human single-chain antibody (ScFv) AIFNalpha1bScFv01 and corresponding whole antibody AIFNalpha1bIgG01 to human interferon alpha1b (IFNalpha1b) with high specificity and high affinity. The IgG antibody could down-regulate the expression of ISG15 and IFIT-1 induced by either recombinant IFNalpha1b or naive IFNalpha from SLE patients' sera, and reduced total serum IgG and IgM antibodies level in a pristane-primed lupus-like mouse model. The crystal structure of AIFNalpha1bScFv01-IFNalpha1b complex solved to 2.8 A resolution revealed that both Pro26-Gln40 region in loop AB and Glu147-Arg150 region in helix E of IFNalpha1b contribute to binding with AIFNalpha1bScFv01. Four residues of above two regions (Leu30, Asp32, Asp35 and Arg150) are critical for the formation of antigen-antibody complexes. AIFNalpha1bScFv01 shares partial epitopes of IFNalpha1b with its receptor IFNAR2 but with much higher binding affinity to IFNalpha1b than IFNAR2. Thus, AIFNalpha1bIgG01 exhibits its neutralizing activity through competition with IFNAR2 to bind with IFNalpha and prevents the activation of IFNalpha-mediated signaling pathway. Our results highlight the potential use of the human antibody for modulating the activity of IFNalpha in SLE. Structural insights into a human anti-IFN antibody exerting therapeutic potential for systemic lupus erythematosus.,Ouyang S, Gong B, Li JZ, Zhao LX, Wu W, Zhang FS, Sun L, Wang SJ, Pan M, Li C, Liang W, Shaw N, Zheng J, Zhao GP, Wang Y, Liu ZJ, Liang M J Mol Med (Berl). 2012 Feb 4. PMID:22307521[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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