View source for 5mj3


==INTERLEUKIN-23 COMPLEX WITH AN ANTAGONISTIC ALPHABODY, CRYSTAL FORM 1==
<StructureSection load='5mj3' size='340' side='right'caption='[[5mj3]], [[Resolution|resolution]] 1.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mj3]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4oe8 4oe8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MJ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MJ3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.74&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5mj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mj3 OCA], [https://pdbe.org/5mj3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mj3 RCSB], [https://www.ebi.ac.uk/pdbsum/5mj3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mj3 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IL12B_HUMAN IL12B_HUMAN] Defects in IL12B are a cause of Mendelian susceptibility to mycobacterial disease (MSMD) [MIM:[https://omim.org/entry/209950 209950]; also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity, whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance.<ref>PMID:9854038</ref> <ref>PMID:11753820</ref>   Genetic variations in IL12B are a cause of susceptibility to psoriasis type 11 (PSORS11) [MIM:[https://omim.org/entry/612599 612599]. Psoriasis is a common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.<ref>PMID:9854038</ref> <ref>PMID:11753820</ref> 
== Function ==
[https://www.uniprot.org/uniprot/IL12B_HUMAN IL12B_HUMAN] Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.<ref>PMID:11114383</ref>   Associates with IL23A to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis.<ref>PMID:11114383</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein scaffolds can provide a promising alternative to antibodies for various biomedical and biotechnological applications, including therapeutics. Here we describe the design and development of the Alphabody, a protein scaffold featuring a single-chain antiparallel triple-helix coiled-coil fold. We report affinity-matured Alphabodies with favourable physicochemical properties that can specifically neutralize human interleukin (IL)-23, a pivotal therapeutic target in autoimmune inflammatory diseases such as psoriasis and multiple sclerosis. The crystal structure of human IL-23 in complex with an affinity-matured Alphabody reveals how the variable interhelical groove of the scaffold uniquely targets a large epitope on the p19 subunit of IL-23 to harness fully the hydrophobic and hydrogen-bonding potential of tryptophan and tyrosine residues contributed by p19 and the Alphabody, respectively. Thus, Alphabodies are suitable for targeting protein-protein interfaces of therapeutic importance and can be tailored to interrogate desired design and binding-mode principles via efficient selection and affinity-maturation strategies.

Structural basis of IL-23 antagonism by an Alphabody protein scaffold.,Desmet J, Verstraete K, Bloch Y, Lorent E, Wen Y, Devreese B, Vandenbroucke K, Loverix S, Hettmann T, Deroo S, Somers K, Henderikx P, Lasters I, Savvides SN Nat Commun. 2014 Oct 30;5:5237. doi: 10.1038/ncomms6237. PMID:25354530<ref>PMID:25354530</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mj3" style="background-color:#fffaf0;"></div>

==See Also==
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Bloch Y]]
[[Category: Deroo S]]
[[Category: Desmet J]]
[[Category: Devreese B]]
[[Category: Hendrikx P]]
[[Category: Hettmann T]]
[[Category: Lasters I]]
[[Category: Lorent E]]
[[Category: Loverix S]]
[[Category: Savvides SN]]
[[Category: Somers K]]
[[Category: Vandenbroucke K]]
[[Category: Verstraete K]]
[[Category: Wen Y]]