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| | ==proIAPP in DPC Micelles - Two-Conformer Ensemble Refinement, Bent Conformer== | | ==proIAPP in DPC Micelles - Two-Conformer Ensemble Refinement, Bent Conformer== |
| - | <StructureSection load='6uck' size='340' side='right'caption='[[6uck]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6uck' size='340' side='right'caption='[[6uck]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6uck]] 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=6UCK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UCK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6uck]] 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=6UCK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UCK FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ua0|6ua0]], [[6ucj|6ucj]]</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6uck FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uck OCA], [https://pdbe.org/6uck PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uck RCSB], [https://www.ebi.ac.uk/pdbsum/6uck PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uck 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=6uck FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uck OCA], [http://pdbe.org/6uck PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uck RCSB], [http://www.ebi.ac.uk/pdbsum/6uck PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uck 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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Banerjee, I]] | + | [[Category: Banerjee I]] |
| - | [[Category: DeLisle, C F]] | + | [[Category: DeLisle CF]] |
| - | [[Category: Lorieau, J L]] | + | [[Category: Lorieau JL]] |
| - | [[Category: Malooley, A L]] | + | [[Category: Malooley AL]] |
| - | [[Category: Amyloid]]
| + | |
| - | [[Category: Hormone]]
| + | |
| - | [[Category: Idp]]
| + | |
| - | [[Category: Membrane-binding]]
| + | |
| 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
Pro-islet amyloid polypeptide (proIAPP) is the prohormone precursor molecule to IAPP, also known as amylin. IAPP is a calcitonin family peptide hormone that is co-secreted with insulin, and largely responsible for hunger satiation and metabolic homeostasis. Amyloid plaques containing mixtures of mature IAPP and misprocessed proIAPP deposit on, and destroy pancreatic beta cell membranes, and they are recognized as a clinical hallmark of type 2 diabetes mellitus. In order to better understand the interaction with cellular membranes, we solved the solution NMR structure of proIAPP bound to dodecylphosphocholine micelles at pH 4.5. We show that proIAPP is a dynamic molecule with four alpha-helices. The first two helices are contained within the mature IAPP sequence, while the second two helices are part of the C-terminal prohormone segment (Cpro). We mapped the membrane topology of the amphipathic helices by paramagnetic relaxation enhancement, and we used circular dichroism and diffusion-ordered spectroscopy to identify environmental factors that impact proIAPP membrane affinity. We discuss how our structural results relate to prohormone processing based on the varied pH environments and lipid compositions of organelle membranes within the regulated secretory pathway, and the likelihood of Cpro survival for co-secretion with IAPP.
Pro-Islet Amyloid Polypeptide in Micelles Contains a Helical Prohormone Segment.,DeLisle CF, Malooley AL, Banerjee I, Lorieau JL FEBS J. 2020 Feb 19. doi: 10.1111/febs.15253. PMID:32077246[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ DeLisle CF, Malooley AL, Banerjee I, Lorieau JL. Pro-Islet Amyloid Polypeptide in Micelles Contains a Helical Prohormone Segment. FEBS J. 2020 Feb 19. doi: 10.1111/febs.15253. PMID:32077246 doi:http://dx.doi.org/10.1111/febs.15253
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