7k7a

From Proteopedia

(Difference between revisions)

Current revision

Transmembrane structure of TNFR1

Structural highlights

7k7a is a 3 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TNR1A_HUMAN Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:142680; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.^[1] ^[2] ^[3] ^[4] ^[5] Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:614810. 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=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.^[6]

Function

TNR1A_HUMAN Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.

Publication Abstract from PubMed

Receptors in the tumor necrosis factor receptor superfamily (TNFRSF) regulate proliferation of immune cells or induce programmed cell death, and many of them are candidates for antibody-based immunotherapy. Previous studies on several death receptors in the TNFRSF including Fas, p75NTR, and DR5 showed that the transmembrane helix (TMH) of these receptors can specifically oligomerize and their oligomeric states have direct consequences on receptor activation, suggesting a much more active role of TMH in receptor signaling than previously appreciated. Here, we report the structure of the TMH of TNFR1, another well studied member of the TNFRSF, in neutral bicelles that mimic a lipid bilayer. We find that TNFR1 TMH forms a defined trimeric complex in bicelles, and no evidences of higher-order clustering of trimers have been detected. Unexpectedly, a conserved proline, which is critical for Fas TMH trimerization, does not appear to play an important role in TNFR1 TMH trimerization, which is instead mediated by a glycine near the middle of the TMH. Further, TNFR1 TMH trimer shows a larger hydrophobic core than that of Fas or DR5, with four layers of hydrophobic interaction along the threefold axis. Comparison of the TNFR1 TMH structure with that of Fas and DR5 reveals reassuring similarities that have functional implications but also significant structural diversity that warrants systematic investigation of TMH oligomerization property for other members of the TNFRSF.

The Diversity and Similarity of Transmembrane Trimerization of TNF Receptors.,Zhao L, Fu Q, Pan L, Piai A, Chou JJ Front Cell Dev Biol. 2020 Oct 14;8:569684. doi: 10.3389/fcell.2020.569684., eCollection 2020. PMID:33163490^[7]

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

References

↑ McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, Mansfield E, Gadina M, Karenko L, Pettersson T, McCarthy J, Frucht DM, Aringer M, Torosyan Y, Teppo AM, Wilson M, Karaarslan HM, Wan Y, Todd I, Wood G, Schlimgen R, Kumarajeewa TR, Cooper SM, Vella JP, Amos CI, Mulley J, Quane KA, Molloy MG, Ranki A, Powell RJ, Hitman GA, O'Shea JJ, Kastner DL. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 1999 Apr 2;97(1):133-44. PMID:10199409
↑ Dode C, Papo T, Fieschi C, Pecheux C, Dion E, Picard F, Godeau P, Bienvenu J, Piette JC, Delpech M, Grateau G. A novel missense mutation (C30S) in the gene encoding tumor necrosis factor receptor 1 linked to autosomal-dominant recurrent fever with localized myositis in a French family. Arthritis Rheum. 2000 Jul;43(7):1535-42. PMID:10902757 doi:<1535::AID-ANR18>3.0.CO;2-C 10.1002/1529-0131(200007)43:7<1535::AID-ANR18>3.0.CO;2-C
↑ Aksentijevich I, Galon J, Soares M, Mansfield E, Hull K, Oh HH, Goldbach-Mansky R, Dean J, Athreya B, Reginato AJ, Henrickson M, Pons-Estel B, O'Shea JJ, Kastner DL. The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. Am J Hum Genet. 2001 Aug;69(2):301-14. Epub 2001 Jul 6. PMID:11443543 doi:S0002-9297(07)61077-5
↑ Aganna E, Hammond L, Hawkins PN, Aldea A, McKee SA, van Amstel HK, Mischung C, Kusuhara K, Saulsbury FT, Lachmann HJ, Bybee A, McDermott EM, La Regina M, Arostegui JI, Campistol JM, Worthington S, High KP, Molloy MG, Baker N, Bidwell JL, Castaner JL, Whiteford ML, Janssens-Korpola PL, Manna R, Powell RJ, Woo P, Solis P, Minden K, Frenkel J, Yague J, Mirakian RM, Hitman GA, McDermott MF. Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes. Arthritis Rheum. 2003 Sep;48(9):2632-44. PMID:13130484 doi:10.1002/art.11215
↑ Kusuhara K, Nomura A, Nakao F, Hara T. Tumour necrosis factor receptor-associated periodic syndrome with a novel mutation in the TNFRSF1A gene in a Japanese family. Eur J Pediatr. 2004 Jan;163(1):30-2. Epub 2003 Nov 11. PMID:14610673 doi:10.1007/s00431-003-1338-0
↑ Gregory AP, Dendrou CA, Attfield KE, Haghikia A, Xifara DK, Butter F, Poschmann G, Kaur G, Lambert L, Leach OA, Promel S, Punwani D, Felce JH, Davis SJ, Gold R, Nielsen FC, Siegel RM, Mann M, Bell JI, McVean G, Fugger L. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature. 2012 Aug 23;488(7412):508-11. doi: 10.1038/nature11307. PMID:22801493 doi:10.1038/nature11307
↑ Zhao L, Fu Q, Pan L, Piai A, Chou JJ. The Diversity and Similarity of Transmembrane Trimerization of TNF Receptors. Front Cell Dev Biol. 2020 Oct 14;8:569684. doi: 10.3389/fcell.2020.569684., eCollection 2020. PMID:33163490 doi:http://dx.doi.org/10.3389/fcell.2020.569684

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/7k7a"

Categories: Homo sapiens | Large Structures | Chou J | Zhao L

@@ Line 1: / Line 1: @@
 ==Transmembrane structure of TNFR1==
-<StructureSection load='7k7a' size='340' side='right'caption='[[7k7a]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
+<StructureSection load='7k7a' size='340' side='right'caption='[[7k7a]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7k7a]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K7A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7K7A FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7k7a]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K7A FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFRSF1A, TNFAR, TNFR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</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=7k7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k7a OCA], [https://pdbe.org/7k7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k7a RCSB], [https://www.ebi.ac.uk/pdbsum/7k7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k7a 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=7k7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k7a OCA], [http://pdbe.org/7k7a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7k7a RCSB], [http://www.ebi.ac.uk/pdbsum/7k7a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7k7a ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[http://omim.org/entry/142680 142680]]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref> <ref>PMID:10902757</ref> <ref>PMID:11443543</ref> <ref>PMID:13130484</ref> <ref>PMID:14610673</ref>   Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[http://omim.org/entry/614810 614810]]. 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=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>
+[https://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[https://omim.org/entry/142680 142680]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref> <ref>PMID:10902757</ref> <ref>PMID:11443543</ref> <ref>PMID:13130484</ref> <ref>PMID:14610673</ref>   Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[https://omim.org/entry/614810 614810]. 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=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.
+[https://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN] Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 19: @@
 </div>
 <div class="pdbe-citations 7k7a" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chou, J]]
+[[Category: Chou J]]
-[[Category: Zhao, L]]
+[[Category: Zhao L]]
-[[Category: Apoptosis]]
-[[Category: Transmembrane helix]]

7k7a

From Proteopedia

Current revision

Transmembrane structure of TNFR1

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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