3j9p
From Proteopedia
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==Structure of the TRPA1 ion channel determined by electron cryo-microscopy== | ==Structure of the TRPA1 ion channel determined by electron cryo-microscopy== | ||
| - | < | + | <SX load='3j9p' size='340' side='right' viewer='molstar' caption='[[3j9p]], [[Resolution|resolution]] 4.24Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3j9p]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J9P OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[3j9p]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J9P FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </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=3j9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j9p OCA], [https://pdbe.org/3j9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j9p RCSB], [https://www.ebi.ac.uk/pdbsum/3j9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j9p ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/TRPA1_HUMAN TRPA1_HUMAN] Familial episodic pain syndrome with predominantly upper body involvement. The disease is caused by mutations affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.[https://www.uniprot.org/uniprot/TRPA1_HUMAN TRPA1_HUMAN] Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).[UniProtKB:Q8BLA8]<ref>PMID:20547126</ref> <ref>PMID:25389312</ref> <ref>PMID:25855297</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The TRPA1 ion channel (also known as the wasabi receptor) is a detector of noxious chemical agents encountered in our environment or produced endogenously during tissue injury or drug metabolism. These include a broad class of electrophiles that activate the channel through covalent protein modification. TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions provoked or exacerbated by irritant exposure. Despite compelling reasons to understand TRPA1 function, structural mechanisms underlying channel regulation remain obscure. Here we use single-particle electron cryo- microscopy to determine the structure of full-length human TRPA1 to approximately 4 A resolution in the presence of pharmacophores, including a potent antagonist. Several unexpected features are revealed, including an extensive coiled-coil assembly domain stabilized by polyphosphate co-factors and a highly integrated nexus that converges on an unpredicted transient receptor potential (TRP)-like allosteric domain. These findings provide new insights into the mechanisms of TRPA1 regulation, and establish a blueprint for structure-based design of analgesic and anti-inflammatory agents. | ||
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| + | Structure of the TRPA1 ion channel suggests regulatory mechanisms.,Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D Nature. 2015 Apr 8. doi: 10.1038/nature14367. PMID:25855297<ref>PMID:25855297</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3j9p" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
| - | </ | + | </SX> |
| - | [[Category: | + | [[Category: Escherichia coli]] |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Armache J-P]] |
| - | [[Category: | + | [[Category: Cheng Y]] |
| - | [[Category: | + | [[Category: Gao Y]] |
| - | [[Category: | + | [[Category: Julius D]] |
| - | [[Category: | + | [[Category: Paulsen CE]] |
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Current revision
Structure of the TRPA1 ion channel determined by electron cryo-microscopy
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