View source for 8di2


==Site 2 insulin receptor binding peptide IM459N21==
<StructureSection load='8di2' size='340' side='right'caption='[[8di2]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8di2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DI2 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</scene>, <scene name='pdbligand=BVK:2-[4-(aminomethyl)phenyl]ethanoic+acid'>BVK</scene>, <scene name='pdbligand=LYN:2,6-DIAMINO-HEXANOIC+ACID+AMIDE'>LYN</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=8di2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8di2 OCA], [https://pdbe.org/8di2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8di2 RCSB], [https://www.ebi.ac.uk/pdbsum/8di2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8di2 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The human insulin receptor signalling system plays a critical role in glucose homeostasis. Insulin binding brings about extensive conformational change in the receptor extracellular region that in turn effects trans-activation of the intracellular tyrosine kinase domains and downstream signalling. Of particular therapeutic interest is whether insulin receptor signalling can be replicated by molecules other than insulin. Here, we present single-particle cryoEM structures that show how a 33-mer polypeptide unrelated to insulin can cross-link two sites on the receptor surface and direct the receptor into a signalling-active conformation. The 33-mer polypeptide engages the receptor by two helical binding motifs that are each potentially mimicable by small molecules. The resultant conformation of the receptor is distinct from-but related to-those in extant three-dimensional structures of the insulin-complexed receptor. Our findings thus illuminate unexplored pathways for controlling the signalling of the insulin receptor as well as opportunities for development of insulin mimetics.

Activation of the human insulin receptor by non-insulin-related peptides.,Kirk NS, Chen Q, Wu YG, Asante AL, Hu H, Espinosa JF, Martinez-Olid F, Margetts MB, Mohammed FA, Kiselyov VV, Barrett DG, Lawrence MC Nat Commun. 2022 Sep 28;13(1):5695. doi: 10.1038/s41467-022-33315-8. PMID:36171189<ref>PMID:36171189</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 8di2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Espinosa JF]]
[[Category: Hu H]]
[[Category: Lawrence MC]]
[[Category: Martinez FJ]]