2l3o

From Proteopedia

(Difference between revisions)

Current revision

Solution structure of murine interleukin 3

Structural highlights

2l3o is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IL3_MOUSE Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells. Stimulates also mature basophils, eosinophils, and monocytes to become functionally activated. In addition, plays an important role in neural cell proliferation and survival. Participates as well in bone homeostasis and inhibits osteoclast differentiation by preventing NF-kappa-B nuclear translocation and activation. Mechanistically, exerts its biological effects through a receptor composed of IL3RA subunit and a signal transducing subunit IL3RB (By similarity). Receptor stimulation results in the rapid activation of JAK2 kinase activity leading to STAT5-mediated transcriptional program (PubMed:10376805, PubMed:31990690, PubMed:8378315). Alternatively, contributes to cell survival under oxidative stress in non-hematopoietic systems by activating pathways mediated by PI3K/AKT and ERK (By similarity).[UniProtKB:P08700]^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Interleukin-3 (IL-3), a cytokine produced primarily by activated T-cells during immune responses, is a crucial regulator of allergic inflammation. The three-dimensional structure of murine IL-3 (mIL-3) has remained elusive owing to its poor solubility and strong tendency toward aggregation under solution conditions typically used for structural studies. Here we describe the solution properties and structure of mIL-3 determined by NMR using an engineered construct of mIL-3 (mIL-3(33-156)). mIL-3 adopts a four-helical bundle fold, typical of proteins belonging to the short-chain cytokine family, and features a core of highly conserved hydrophobic residues. While significant line broadening and peak disappearance were observed in NMR spectra at higher temperatures, there was no evidence for temperature-dependent changes of the oligomeric state of mIL-3(33-156). Further analysis of the temperature dependence of amide (1)H chemical shifts and backbone (15)N relaxation parameters, including (15)N relaxation dispersion, revealed the presence of significant conformational exchange and local conformational heterogeneity. Residues recently shown by mutagenesis to play key roles in beta(IL-3) receptor recognition and activation, which are located within the alpha(A) and alpha(C) helices and aligned on one face of the mIL-3(33-156) structure, are relatively rigid. In contrast, pronounced conformational heterogeneity was observed for a cluster of residues located on the opposite side of mIL-3, which corresponds spatially to sites in the related cytokines human IL-3, IL-5, and GM-CSF that are known to mediate interactions with their respective alpha-receptor subunits. Such conformational heterogeneity may facilitate the interaction of mIL-3 with each of two naturally occurring mIL-3Ralpha isoforms, leading to structurally distinct high-affinity complexes.

Murine interleukin-3: structure, dynamics, and conformational heterogeneity in solution.,Yao S, Young IG, Norton RS, Murphy JM Biochemistry. 2011 Apr 5;50(13):2464-77. Epub 2011 Mar 2. PMID:21329364^[5]

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

References

↑ Jaster R, Tschirch E, Bittorf T, Brock J. Role of STAT5 in interferon-alpha signal transduction in Ba/F3 cells. Cell Signal. 1999 May;11(5):331-5. doi: 10.1016/s0898-6568(98)00049-7. PMID:10376805 doi:http://dx.doi.org/10.1016/s0898-6568(98)00049-7
↑ Tong Y, Lear TB, Evankovich J, Chen Y, Londino JD, Myerburg MM, Zhang Y, Popescu ID, McDyer JF, McVerry BJ, Lockwood KC, Jurczak MJ, Liu Y, Chen BB. The RNFT2/IL-3Rα axis regulates IL-3 signaling and innate immunity. JCI Insight. 2020 Feb 13;5(3):e133652. PMID:31990690 doi:10.1172/jci.insight.133652
↑ Silvennoinen O, Witthuhn BA, Quelle FW, Cleveland JL, Yi T, Ihle JN. Structure of the murine Jak2 protein-tyrosine kinase and its role in interleukin 3 signal transduction. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8429-33. PMID:8378315
↑ Mach N, Lantz CS, Galli SJ, Reznikoff G, Mihm M, Small C, Granstein R, Beissert S, Sadelain M, Mulligan RC, Dranoff G. Involvement of interleukin-3 in delayed-type hypersensitivity. Blood. 1998 Feb 1;91(3):778-83. PMID:9446636
↑ Yao S, Young IG, Norton RS, Murphy JM. Murine interleukin-3: structure, dynamics, and conformational heterogeneity in solution. Biochemistry. 2011 Apr 5;50(13):2464-77. Epub 2011 Mar 2. PMID:21329364 doi:10.1021/bi101810f

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2l3o"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2l3o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L3O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L3O FirstGlance]. <br>
-</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=2l3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l3o OCA], [https://pdbe.org/2l3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l3o RCSB], [https://www.ebi.ac.uk/pdbsum/2l3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l3o ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=2l3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l3o OCA], [https://pdbe.org/2l3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l3o RCSB], [https://www.ebi.ac.uk/pdbsum/2l3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l3o ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/IL3_MOUSE IL3_MOUSE] Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells. Stimulates also mature basophils, eosinophils, and monocytes to become functionally activated. In addition, plays an important role in neural cell proliferation and survival. Participates as well in bone homeostasis and inhibits osteoclast differentiation by preventing NF-kappa-B nuclear translocation and activation. Mechanistically, exerts its biological effects through a receptor composed of IL3RA subunit and a signal transducing subunit IL3RB (By similarity). Receptor stimulation results in the rapid activation of JAK2 kinase activity leading to STAT5-mediated transcriptional program (PubMed:8378315, PubMed:10376805). Alternatively, contributes to cell survival under oxidative stress in non-hematopoietic systems by activating pathways mediated by PI3K/AKT and ERK (By similarity).[UniProtKB:P08700]<ref>PMID:10376805</ref> <ref>PMID:8378315</ref> <ref>PMID:9446636</ref>
+[https://www.uniprot.org/uniprot/IL3_MOUSE IL3_MOUSE] Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells. Stimulates also mature basophils, eosinophils, and monocytes to become functionally activated. In addition, plays an important role in neural cell proliferation and survival. Participates as well in bone homeostasis and inhibits osteoclast differentiation by preventing NF-kappa-B nuclear translocation and activation. Mechanistically, exerts its biological effects through a receptor composed of IL3RA subunit and a signal transducing subunit IL3RB (By similarity). Receptor stimulation results in the rapid activation of JAK2 kinase activity leading to STAT5-mediated transcriptional program (PubMed:10376805, PubMed:31990690, PubMed:8378315). Alternatively, contributes to cell survival under oxidative stress in non-hematopoietic systems by activating pathways mediated by PI3K/AKT and ERK (By similarity).[UniProtKB:P08700]<ref>PMID:10376805</ref> <ref>PMID:31990690</ref> <ref>PMID:8378315</ref> <ref>PMID:9446636</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

2l3o

From Proteopedia

Current revision

Solution structure of murine interleukin 3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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