View source for 6zrq


==two-protofilament amyloid structure of S20G variant of human amylin (IAPP - islet amyloid polypeptide)==
<StructureSection load='6zrq' size='340' side='right'caption='[[6zrq]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZRQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TYC:L-TYROSINAMIDE'>TYC</scene></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=6zrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zrq OCA], [https://pdbe.org/6zrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zrq RCSB], [https://www.ebi.ac.uk/pdbsum/6zrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zrq ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Aggregation of the peptide hormone amylin into amyloid deposits is a pathological hallmark of type-2 diabetes (T2D). While no causal link between T2D and amyloid has been established, the S20G mutation in amylin is associated with early-onset T2D. Here we report cryo-EM structures of amyloid fibrils of wild-type human amylin and its S20G variant. The wild-type fibril structure, solved to 3.6-A resolution, contains two protofilaments, each built from S-shaped subunits. S20G fibrils, by contrast, contain two major polymorphs. Their structures, solved at 3.9-A and 4.0-A resolution, respectively, share a common two-protofilament core that is distinct from the wild-type structure. Remarkably, one polymorph contains a third subunit with another, distinct, cross-beta conformation. The presence of two different backbone conformations within the same fibril may explain the increased aggregation propensity of S20G, and illustrates a potential structural basis for surface-templated fibril assembly.

Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly.,Gallardo R, Iadanza MG, Xu Y, Heath GR, Foster R, Radford SE, Ranson NA Nat Struct Mol Biol. 2020 Sep 14. pii: 10.1038/s41594-020-0496-3. doi:, 10.1038/s41594-020-0496-3. PMID:32929282<ref>PMID:32929282</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Gallardo RU]]
[[Category: Iadanza MG]]
[[Category: Radford SE]]
[[Category: Ranson NA]]