7sl7: Difference between revisions
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==Full-length insulin receptor bound with both site 1 binding deficient mutant insulin (A-V3E) and site 2 binding deficient mutant insulin (A-L13R)== | |||
<StructureSection load='7sl7' size='340' side='right'caption='[[7sl7]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7sl7]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SL7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SL7 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]] 3.1Å</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=7sl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sl7 OCA], [https://pdbe.org/7sl7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sl7 RCSB], [https://www.ebi.ac.uk/pdbsum/7sl7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sl7 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Gamma-shaped conformation. IR with two insulins bound assumes a T-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the T-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation. | |||
Synergistic activation of the insulin receptor via two distinct sites.,Li J, Park J, Mayer JP, Webb KJ, Uchikawa E, Wu J, Liu S, Zhang X, Stowell MHB, Choi E, Bai XC Nat Struct Mol Biol. 2022 Apr;29(4):357-368. doi: 10.1038/s41594-022-00750-6. , Epub 2022 Mar 31. PMID:35361965<ref>PMID:35361965</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7sl7" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Insulin receptor 3D structures|Insulin receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Bai XC]] | |||
[[Category: Choi E]] | |||
Latest revision as of 12:10, 17 October 2024
Full-length insulin receptor bound with both site 1 binding deficient mutant insulin (A-V3E) and site 2 binding deficient mutant insulin (A-L13R)Full-length insulin receptor bound with both site 1 binding deficient mutant insulin (A-V3E) and site 2 binding deficient mutant insulin (A-L13R)
Structural highlights
Publication Abstract from PubMedInsulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Gamma-shaped conformation. IR with two insulins bound assumes a T-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the T-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation. Synergistic activation of the insulin receptor via two distinct sites.,Li J, Park J, Mayer JP, Webb KJ, Uchikawa E, Wu J, Liu S, Zhang X, Stowell MHB, Choi E, Bai XC Nat Struct Mol Biol. 2022 Apr;29(4):357-368. doi: 10.1038/s41594-022-00750-6. , Epub 2022 Mar 31. PMID:35361965[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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