6y1a: Difference between revisions

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== 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.

== Publication Abstract from PubMed ==

Amyloid deposits consisting of fibrillar islet amyloid polypeptide (IAPP) in pancreatic islets are associated with beta-cell loss and have been implicated in type 2 diabetes (T2D). Here, we applied cryo-EM to reconstruct densities of three dominant IAPP fibril polymorphs, formed in vitro from synthetic human IAPP. An atomic model of the main polymorph, built from a density map of 4.2-A resolution, reveals two S-shaped, intertwined protofilaments. The segment 21-NNFGAIL-27, essential for IAPP amyloidogenicity, forms the protofilament interface together with Tyr37 and the amidated C terminus. The S-fold resembles polymorphs of Alzheimer's disease (AD)-associated amyloid-beta (Abeta) fibrils, which might account for the epidemiological link between T2D and AD and reports on IAPP-Abeta cross-seeding in vivo. The results structurally link the early-onset T2D IAPP genetic polymorphism (encoding Ser20Gly) with the AD Arctic mutation (Glu22Gly) of Abeta and support the design of inhibitors and imaging probes for IAPP fibrils.

Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-beta fibrils.,Roder C, Kupreichyk T, Gremer L, Schafer LU, Pothula KR, Ravelli RBG, Willbold D, Hoyer W, Schroder GF Nat Struct Mol Biol. 2020 Jul;27(7):660-667. doi: 10.1038/s41594-020-0442-4. Epub, 2020 Jun 15. PMID:32541895<ref>PMID:32541895</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

== References ==

__TOC__

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@@ Line 9: / Line 9: @@
 == 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Amyloid deposits consisting of fibrillar islet amyloid polypeptide (IAPP) in pancreatic islets are associated with beta-cell loss and have been implicated in type 2 diabetes (T2D). Here, we applied cryo-EM to reconstruct densities of three dominant IAPP fibril polymorphs, formed in vitro from synthetic human IAPP. An atomic model of the main polymorph, built from a density map of 4.2-A resolution, reveals two S-shaped, intertwined protofilaments. The segment 21-NNFGAIL-27, essential for IAPP amyloidogenicity, forms the protofilament interface together with Tyr37 and the amidated C terminus. The S-fold resembles polymorphs of Alzheimer's disease (AD)-associated amyloid-beta (Abeta) fibrils, which might account for the epidemiological link between T2D and AD and reports on IAPP-Abeta cross-seeding in vivo. The results structurally link the early-onset T2D IAPP genetic polymorphism (encoding Ser20Gly) with the AD Arctic mutation (Glu22Gly) of Abeta and support the design of inhibitors and imaging probes for IAPP fibrils.
+Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-beta fibrils.,Roder C, Kupreichyk T, Gremer L, Schafer LU, Pothula KR, Ravelli RBG, Willbold D, Hoyer W, Schroder GF Nat Struct Mol Biol. 2020 Jul;27(7):660-667. doi: 10.1038/s41594-020-0442-4. Epub, 2020 Jun 15. PMID:32541895<ref>PMID:32541895</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6y1a" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </SX>