View source for 6ucj


==proIAPP in DPC Micelles - Two-Conformer Ensemble Refinement, Open Conformer==
<StructureSection load='6ucj' size='340' side='right'caption='[[6ucj]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ucj]] 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=6UCJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UCJ FirstGlance]. <br>
</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ucj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ucj OCA], [https://pdbe.org/6ucj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ucj RCSB], [https://www.ebi.ac.uk/pdbsum/6ucj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ucj ProSAT]</span></td></tr>
</table>
== Function ==
[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.
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== 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<ref>PMID:32077246</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6ucj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Banerjee I]]
[[Category: DeLisle CF]]
[[Category: Lorieau JL]]
[[Category: Malooley AL]]