2m2f
From Proteopedia
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| - | + | ==The membran-proximal domain of ADAM17== | |
| - | === | + | <StructureSection load='2m2f' size='340' side='right' caption='[[2m2f]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[2m2f]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M2F FirstGlance]. <br> | |
| - | ==Disease== | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADAM17, CSVP, TACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> |
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/ADAM_17_endopeptidase ADAM 17 endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.86 3.4.24.86] </span></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=2m2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m2f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2m2f RCSB], [http://www.ebi.ac.uk/pdbsum/2m2f PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[http://www.uniprot.org/uniprot/ADA17_HUMAN ADA17_HUMAN]] Defects in ADAM17 are a cause of neonatal inflammatory skin and bowel disease (NISBD) [MIM:[http://omim.org/entry/614328 614328]]. NISBD is a disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.<ref>PMID:22010916</ref> | [[http://www.uniprot.org/uniprot/ADA17_HUMAN ADA17_HUMAN]] Defects in ADAM17 are a cause of neonatal inflammatory skin and bowel disease (NISBD) [MIM:[http://omim.org/entry/614328 614328]]. NISBD is a disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.<ref>PMID:22010916</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ADA17_HUMAN ADA17_HUMAN]] Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Also involved in the activation of Notch pathway (By similarity).<ref>PMID:12441351</ref> <ref>PMID:20592283</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A disintegrin and metalloprotease-17 (ADAM17) is a major sheddase responsible for the regulation of a wide range of biological processes, like cellular differentiation, regeneration, or cancer progression. Hitherto, the mechanism regulating the enzymatic activity of ADAM17 is poorly understood. Recently, protein-disulfide isomerase (PDI) was shown to interact with ADAM17 and to down-regulate its enzymatic activity. Here we demonstrate by NMR spectroscopy and tandem-mass spectrometry that PDI directly interacts with the membrane-proximal domain (MPD), a domain of ADAM17 involved in its dimerization and substrate recognition. PDI catalyzes an isomerization of disulfide bridges within the thioredoxin motif C600XXC603 of the MPD and results in a drastic structural change between an active open state and an inactive closed conformation. This conformational change of the MPD putatively acts as a molecular switch, facilitating a global reorientation of the extracellular domains in ADAM17 and regulating its shedding activity. | ||
| - | + | Membrane-Proximal Domain of a Disintegrin and Metalloprotease-17 Represents the Putative Molecular Switch of Its Shedding Activity Operated by Protein-disulfide Isomerase.,Dusterhoft S, Jung S, Hung CW, Tholey A, Sonnichsen FD, Grotzinger J, Lorenzen I J Am Chem Soc. 2013 Apr 5. PMID:23521534<ref>PMID:23521534</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | ==See Also== |
| - | + | *[[A Disintegrin And Metalloproteinase|A Disintegrin And Metalloproteinase]] | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: ADAM 17 endopeptidase]] | [[Category: ADAM 17 endopeptidase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Duesterhoeft, S | + | [[Category: Duesterhoeft, S]] |
| - | [[Category: Groetzinger, J | + | [[Category: Groetzinger, J]] |
| - | [[Category: Hung, C | + | [[Category: Hung, C]] |
| - | [[Category: Jung, S | + | [[Category: Jung, S]] |
| - | [[Category: Lorenzen, I | + | [[Category: Lorenzen, I]] |
| - | [[Category: Soennichsen, F D | + | [[Category: Soennichsen, F D]] |
| - | [[Category: Tholey, A | + | [[Category: Tholey, A]] |
[[Category: Adam17]] | [[Category: Adam17]] | ||
[[Category: Closed conformer]] | [[Category: Closed conformer]] | ||
[[Category: Hydrolase regulator]] | [[Category: Hydrolase regulator]] | ||
[[Category: Membrane-proximal domain]] | [[Category: Membrane-proximal domain]] | ||
Revision as of 06:36, 22 December 2014
The membran-proximal domain of ADAM17
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