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5uui

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Crystal Structure of Spin-Labeled T77C TNFa

Structural highlights

5uui is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TNFA_HUMAN] Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:607507]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).

Function

[TNFA_HUMAN] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.^[1] The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.^[2]

Publication Abstract from PubMed

Double electron-electron resonance in conjunction with site-directed spin labeling has been used to probe natural conformational sampling of the human tumor necrosis factor alpha trimer. We suggest a previously unreported, predeoligomerization conformation of the trimer that has been shown to be sampled at low frequency. A model of this trimeric state has been constructed based on crystal structures using the double-electron-electron-resonance distances. The model shows one of the protomers to be rotated and tilted outward at the tip end, leading to a breaking of the trimerous symmetry and distortion at a receptor-binding interface. The new structure offers opportunities to modulate the biological activity of tumor necrosis factor alpha through stabilization of the distorted trimer with small molecules.

Natural Conformational Sampling of Human TNFalpha Visualized by Double Electron-Electron Resonance.,Carrington B, Myers WK, Horanyi P, Calmiano M, Lawson ADG Biophys J. 2017 Jul 25;113(2):371-380. doi: 10.1016/j.bpj.2017.06.007. PMID:28746848^[3]

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

References

↑ Friedmann E, Hauben E, Maylandt K, Schleeger S, Vreugde S, Lichtenthaler SF, Kuhn PH, Stauffer D, Rovelli G, Martoglio B. SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production. Nat Cell Biol. 2006 Aug;8(8):843-8. Epub 2006 Jul 9. PMID:16829952 doi:10.1038/ncb1440
↑ Friedmann E, Hauben E, Maylandt K, Schleeger S, Vreugde S, Lichtenthaler SF, Kuhn PH, Stauffer D, Rovelli G, Martoglio B. SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production. Nat Cell Biol. 2006 Aug;8(8):843-8. Epub 2006 Jul 9. PMID:16829952 doi:10.1038/ncb1440
↑ Carrington B, Myers WK, Horanyi P, Calmiano M, Lawson ADG. Natural Conformational Sampling of Human TNFalpha Visualized by Double Electron-Electron Resonance. Biophys J. 2017 Jul 25;113(2):371-380. doi: 10.1016/j.bpj.2017.06.007. PMID:28746848 doi:http://dx.doi.org/10.1016/j.bpj.2017.06.007

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5uui"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Spin-Labeled T77C TNFa==
-<StructureSection load='5uui' size='340' side='right' caption='[[5uui]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
+<StructureSection load='5uui' size='340' side='right'caption='[[5uui]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5uui]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UUI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UUI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5uui]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UUI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UUI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTN:S-[(1-OXYL-2,2,5,5-TETRAMETHYL-2,5-DIHYDRO-1H-PYRROL-3-YL)METHYL]+METHANESULFONOTHIOATE'>MTN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTN:S-[(1-OXYL-2,2,5,5-TETRAMETHYL-2,5-DIHYDRO-1H-PYRROL-3-YL)METHYL]+METHANESULFONOTHIOATE'>MTN</scene></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=5uui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uui OCA], [http://pdbe.org/5uui PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uui RCSB], [http://www.ebi.ac.uk/pdbsum/5uui PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uui ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5uui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uui OCA], [http://pdbe.org/5uui PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uui RCSB], [http://www.ebi.ac.uk/pdbsum/5uui PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uui ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5uui" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Tumor necrosis factor|Tumor necrosis factor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Ceska, T]]
 [[Category: Dranow, D M]]

5uui

From Proteopedia

Current revision

Crystal Structure of Spin-Labeled T77C TNFa

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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