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| | ==Solution structure of oxidized and amidated human IAPP (1-37), the diabetes II peptide.== | | ==Solution structure of oxidized and amidated human IAPP (1-37), the diabetes II peptide.== |
| - | <StructureSection load='5mgq' size='340' side='right' caption='[[5mgq]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='5mgq' size='340' side='right'caption='[[5mgq]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mgq]] is a 1 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=5MGQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MGQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mgq]] 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=5MGQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MGQ FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYC:L-TYROSINAMIDE'>TYC</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IAPP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=5mgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgq OCA], [http://pdbe.org/5mgq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mgq RCSB], [http://www.ebi.ac.uk/pdbsum/5mgq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgq ProSAT]</span></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=5mgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgq OCA], [https://pdbe.org/5mgq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mgq RCSB], [https://www.ebi.ac.uk/pdbsum/5mgq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IAPP_HUMAN IAPP_HUMAN]] Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. | + | [https://www.uniprot.org/uniprot/IAPP_HUMAN IAPP_HUMAN] Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Camargo, D C.Rodriguez]] | + | [[Category: Large Structures]] |
| - | [[Category: Reif, B]] | + | [[Category: Reif B]] |
| - | [[Category: Tripsianes, K]] | + | [[Category: Rodriguez Camargo DC]] |
| - | [[Category: Protein fibril]] | + | [[Category: Tripsianes K]] |
| - | [[Category: Recombinant human iapp]]
| + | |
| - | [[Category: Type ii diabetes]]
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| Structural highlights
Function
IAPP_HUMAN Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism.
Publication Abstract from PubMed
Type II diabetes (T2D) is characterized by diminished insulin production and resistance of cells to insulin. Among others, endoplasmic reticulum (ER) stress is a principal factor contributing to T2D and induces a shift towards a more reducing cellular environment. At the same time, peripheral insulin resistance triggers the over-production of regulatory hormones such as insulin and human islet amyloid polypeptide (hIAPP). We show that the differential aggregation of reduced and oxidized hIAPP assists to maintain the redox equilibrium by restoring redox equivalents. Aggregation thus induces redox balancing which can assist initially to counteract ER stress. Failure of the protein degradation machinery might finally result in beta-cell disruption and cell death. We further present a structural characterization of hIAPP in solution, demonstrating that the N-terminus of the oxidized peptide has a high propensity to form an alpha-helical structure which is lacking in the reduced state of hIAPP. In healthy cells, this residual structure prevents the conversion into amyloidogenic aggregates.
The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes.,Rodriguez Camargo DC, Tripsianes K, Buday K, Franko A, Gobl C, Hartlmuller C, Sarkar R, Aichler M, Mettenleiter G, Schulz M, Boddrich A, Erck C, Martens H, Walch AK, Madl T, Wanker EE, Conrad M, de Angelis MH, Reif B Sci Rep. 2017 Mar 13;7:44041. doi: 10.1038/srep44041. PMID:28287098[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rodriguez Camargo DC, Tripsianes K, Buday K, Franko A, Gobl C, Hartlmuller C, Sarkar R, Aichler M, Mettenleiter G, Schulz M, Boddrich A, Erck C, Martens H, Walch AK, Madl T, Wanker EE, Conrad M, de Angelis MH, Reif B. The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes. Sci Rep. 2017 Mar 13;7:44041. doi: 10.1038/srep44041. PMID:28287098 doi:http://dx.doi.org/10.1038/srep44041
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