View source for 7tyj


==Cryo-EM Structure of insulin receptor-related receptor (IRR) in apo-state captured at pH 7. The 3D refinement was focused on one of two halves with C1 symmetry applied==
<StructureSection load='7tyj' size='340' side='right'caption='[[7tyj]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7tyj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TYJ 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]] 3.3&#8491;</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=7tyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tyj OCA], [https://pdbe.org/7tyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tyj RCSB], [https://www.ebi.ac.uk/pdbsum/7tyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tyj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/INSRR_HUMAN INSRR_HUMAN] Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB.<ref>PMID:21641549</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The insulin receptor (IR) family is a subfamily of receptor tyrosine kinases that controls metabolic homeostasis and cell growth. Distinct from IR and insulin-like growth factor 1 receptor, whose activation requires ligand binding, insulin receptor-related receptor (IRR)-the third member of the IR family-is activated by alkaline pH. However, the molecular mechanism underlying alkaline pH-induced IRR activation remains unclear. Here, we present cryo-EM structures of human IRR in both neutral pH inactive and alkaline pH active states. Combined with mutagenesis and cellular assays, we show that, upon pH increase, electrostatic repulsion of the pH-sensitive motifs of IRR disrupts its autoinhibited state and promotes a scissor-like rotation between two protomers, leading to a T-shaped active conformation. Together, our study reveals an unprecedented alkaline pH-dependent activation mechanism of IRR, opening up opportunities to understand the structure-function relationship of this important receptor.

Structural basis of the alkaline pH-dependent activation of insulin receptor-related receptor.,Wang L, Hall C, Li J, Choi E, Bai XC Nat Struct Mol Biol. 2023 May;30(5):661-669. doi: 10.1038/s41594-023-00974-0. , Epub 2023 Apr 13. PMID:37055497<ref>PMID:37055497</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7tyj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bai XC]]
[[Category: Choi E]]
[[Category: Hall C]]
[[Category: Li J]]
[[Category: Wang LW]]