View source for 1ich


==SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN==
<StructureSection load='1ich' size='340' side='right'caption='[[1ich]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ich]] is a 1 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=1ICH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ICH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [https://pdbe.org/1ich PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [https://www.ebi.ac.uk/pdbsum/1ich PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ich ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ic/1ich_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ich ConSurf].
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== Publication Abstract from PubMed ==
Tumor necrosis factor receptor-1 death domain (TNFR-1 DD) is the intracellular functional domain responsible for the receptor signaling activities. The solution structure of the R347K mutant of TNFR-1 DD was solved by NMR spectroscopy. A total of 20 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 1167 distance constraints and 117 torsion angle constraints. The atomic rms distribution about the mean coordinate positions for the 20 structures for residues composing the secondary structure region is 0.40 A for the backbone atoms and 1.09 A for all atoms. The structure consists of six antiparallel alpha-helices arranged in a similar fashion to the other members of the death domain superfamily. The secondary structure and three-dimensional structure of R347K TNFR1-DD are very similar to the secondary structure and deduced topology of the R347A TNFR1-DD mutant. Mutagenesis studies identified critical residues located in alpha2 and part of alpha3 and alpha4 that are crucial for self-interaction and interaction with TRADD. Structural superposition with previously solved proteins in the death domain superfamily reveals that the major differences between the structures reside in alpha2, alpha3, and alpha4. Interestingly, these regions correspond to the binding sites of TNFR1-DD, providing a structural basis for the specificity of death domain interactions and its subsequent signaling event.

Solution structure of the tumor necrosis factor receptor-1 death domain.,Sukits SF, Lin LL, Hsu S, Malakian K, Powers R, Xu GY J Mol Biol. 2001 Jul 20;310(4):895-906. PMID:11453696<ref>PMID:11453696</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lin L-L]]
[[Category: Malakian K]]
[[Category: Powers R]]
[[Category: Sukits SF]]
[[Category: Xu G-Y]]