View source for 6p67


==Crystal Structure of a Complex of human IL-7Ralpha with an anti-IL-7Ralpha 2B8 Fab==
<StructureSection load='6p67' size='340' side='right'caption='[[6p67]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6p67]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P67 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]] 2.9&#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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6p67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p67 OCA], [https://pdbe.org/6p67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p67 RCSB], [https://www.ebi.ac.uk/pdbsum/6p67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p67 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IL7RA_HUMAN IL7RA_HUMAN] Defects in IL7R are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID) [MIM:[https://omim.org/entry/608971 608971]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.<ref>PMID:9843216</ref> [:]<ref>PMID:15372022</ref> <ref>PMID:15489334</ref> <ref>PMID:11023514</ref>   Genetic variations in IL7R are a cause of susceptibility to multiple sclerosis type 3 (MS3) [MIM:[https://omim.org/entry/612595 612595]. A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note=A polymorphism at position 244 strongly influences susceptibility to multiple sclerosis. Overtransmission of the major 'C' allele coding for Thr-244 is detected in offspring affected with multiple sclerosis. In vitro analysis of transcripts from minigenes containing either 'C' allele (Thr-244) or 'T' allele (Ile-244) shows that the 'C' allele results in an approximately two-fold increase in the skipping of exon 6, leading to increased production of a soluble form of IL7R. Thus, the multiple sclerosis associated 'C' risk allele of IL7R would probably decrease membrane-bound expression of IL7R. As this risk allele is common in the general population, some additional triggers are probably required for the development and progression of MS.<ref>PMID:17660817</ref> 
== Function ==
[https://www.uniprot.org/uniprot/IL7RA_HUMAN IL7RA_HUMAN] Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pediatric T cell acute lymphoblastic leukemia (T-ALL) cells frequently contain mutations in the interleukin-7 (IL-7) receptor pathway or respond to IL-7 itself. To target the IL-7 receptor on T-ALL cells, murine monoclonal antibodies (MAbs) were developed against the human IL-7Ralpha chain and chimerized with human IgG1 constant regions. Crystal structures demonstrate that the two MAbs bound different IL-7Ralpha epitopes. The MAbs mediated antibody-dependent cell-mediated cytotoxicity (ADCC) against patient-derived xenograft (PDX) T-ALL cells, which was improved by combining two MAbs. In vivo, the MAbs showed therapeutic efficacy via ADCC-dependent and independent mechanisms in minimal residual and established disease. PDX T-ALL cells that relapsed following a course of chemotherapy displayed elevated IL-7Ralpha, and MAb treatment is effective against relapsing disease, suggesting the use of anti-IL7Ralpha MAbs in relapsed T-ALL patients or patients that do not respond to chemotherapy.

New anti-IL-7Ralpha monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models.,Hixon JA, Andrews C, Kashi L, Kohnhorst CL, Senkevitch E, Czarra K, Barata JT, Li W, Schneider JP, Walsh STR, Durum SK Leukemia. 2019 Aug 22. pii: 10.1038/s41375-019-0531-8. doi:, 10.1038/s41375-019-0531-8. PMID:31439943<ref>PMID:31439943</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6p67" style="background-color:#fffaf0;"></div>

==See Also==
*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Kashi L]]
[[Category: Kohnhorst CL]]
[[Category: Walsh STR]]