8ent

From Proteopedia

(Difference between revisions)

Revision as of 21:17, 28 June 2023

Interleukin-21 signaling complex with IL-21R and IL-2Rg

Structural highlights

8ent is a 11 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.83Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IL21_HUMAN Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation.^[1] ^[2]

Publication Abstract from PubMed

Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and association with autoimmune disease. To better understand the structural basis of IL-21 signaling, we determine the structure of the IL-21-IL-21R-gammac ternary signaling complex by X-ray crystallography and a structure of a dimer of trimeric complexes using cryo-electron microscopy. Guided by the structure, we design analogs of IL-21 by introducing substitutions to the IL-21-gammac interface. These IL-21 analogs act as partial agonists that modulate downstream activation of pS6, pSTAT3, and pSTAT1. These analogs exhibit differential activity on T and B cell subsets and modulate antibody production in human tonsil organoids. These results clarify the structural basis of IL-21 signaling and offer a potential strategy for tunable manipulation of humoral immunity.

A structural blueprint for interleukin-21 signal modulation.,Abhiraman GC, Bruun TUJ, Caveney NA, Su LL, Saxton RA, Yin Q, Tang S, Davis MM, Jude KM, Garcia KC Cell Rep. 2023 Jun 19;42(6):112657. doi: 10.1016/j.celrep.2023.112657. PMID:37339051^[3]

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

References

↑ Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper JL, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Rayond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly RD, Foster D. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000 Nov 2;408(6808):57-63. PMID:11081504 doi:http://dx.doi.org/10.1038/35040504
↑ Strengell M, Julkunen I, Matikainen S. IFN-alpha regulates IL-21 and IL-21R expression in human NK and T cells. J Leukoc Biol. 2004 Aug;76(2):416-22. Epub 2004 Jun 3. PMID:15178704 doi:http://dx.doi.org/10.1189/jlb.1003488
↑ Abhiraman GC, Bruun TUJ, Caveney NA, Su LL, Saxton RA, Yin Q, Tang S, Davis MM, Jude KM, Garcia KC. A structural blueprint for interleukin-21 signal modulation. Cell Rep. 2023 Jun 19;42(6):112657. PMID:37339051 doi:10.1016/j.celrep.2023.112657

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/8ent"

Categories: Homo sapiens | Large Structures | Abhiraman GC | Garcia KC | Jude KM

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8ent is ON HOLD  until Paper Publication
+==Interleukin-21 signaling complex with IL-21R and IL-2Rg==
+<StructureSection load='8ent' size='340' side='right'caption='[[8ent]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8ent]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ENT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ENT 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]] 2.83&#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=EDO:1,2-ETHANEDIOL'>EDO</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=8ent FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ent OCA], [https://pdbe.org/8ent PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ent RCSB], [https://www.ebi.ac.uk/pdbsum/8ent PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ent ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/IL21_HUMAN IL21_HUMAN] Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation.<ref>PMID:11081504</ref> <ref>PMID:15178704</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and association with autoimmune disease. To better understand the structural basis of IL-21 signaling, we determine the structure of the IL-21-IL-21R-gammac ternary signaling complex by X-ray crystallography and a structure of a dimer of trimeric complexes using cryo-electron microscopy. Guided by the structure, we design analogs of IL-21 by introducing substitutions to the IL-21-gammac interface. These IL-21 analogs act as partial agonists that modulate downstream activation of pS6, pSTAT3, and pSTAT1. These analogs exhibit differential activity on T and B cell subsets and modulate antibody production in human tonsil organoids. These results clarify the structural basis of IL-21 signaling and offer a potential strategy for tunable manipulation of humoral immunity.
-Authors:
+A structural blueprint for interleukin-21 signal modulation.,Abhiraman GC, Bruun TUJ, Caveney NA, Su LL, Saxton RA, Yin Q, Tang S, Davis MM, Jude KM, Garcia KC Cell Rep. 2023 Jun 19;42(6):112657. doi: 10.1016/j.celrep.2023.112657. PMID:37339051<ref>PMID:37339051</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 8ent" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Abhiraman GC]]
+[[Category: Garcia KC]]
+[[Category: Jude KM]]

8ent

From Proteopedia

Revision as of 21:17, 28 June 2023

Interleukin-21 signaling complex with IL-21R and IL-2Rg

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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