Insulin-like growth factor receptor: Difference between revisions

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Michal Harel, Alexander Berchansky

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-<StructureSection load='3nw6' size='400' side='right' caption='Structure of IGFR I kinase domain complex with inhibitor (PDB entry [[3nw6]])' scene=''>
+<StructureSection load='3i81' size='350' side='right' scene='' caption='Human insulin-like growth factor 1 receptor complex with inhibitor (PDB code [[3i81]])'>
+'''Insulin-like growth factor receptors''' (IGFR) are transmembrane receptors which are stimulated by insulin-like growth factors (IGF).  IGFR contains 2 extracellular α chains and 2 transmembranal β chains.  Upon binding of IGF, a tyrosine in the β chain becomes autophosphorylated and triggers a cascade of intracellular signaling. The insulin-like growth factor 1 (IGF-1) receptor belongs to the large class of [[Receptor tyrosine kinases|tyrosine kinase receptors]]. See also [[IGF1]], [[Growth factors]] and [[Kinase-linked, enzyme-linked and related receptors]].
+*'''Insulin-like growth factor receptor 1''' is the mediator of the anabolic and mitogenic activity of growth hormone<ref>PMID: 11577173</ref><br />
+*'''Insulin-like growth factor receptor 2''' is a protein hormone regulating cell proliferation, growth, migration, differentiation and survival<ref>PMID: 23257688</ref><br />.
+===  Memory-Enhancement by Traditional Chinese Medicine? <ref>doi 10.1080/07391102.2012.741052</ref>===
-'''Insulin-like growth factor receptors''' (IGFR) are transmembrane receptors which are stimulated by insulin-like growth factors (IGF).  IGFR contains 2 extracellular α chains and 2 transmembranal β chains.  Upon binding of IGF, a tyrosine in the β chain becomes autophosphorylated and triggers a cascade of intracellular signaling.
+Cognitive impairment is an emerging issue and increasing research points to the significant role of insulin-like growth factor I (IGF-I) in cognitive brain functions. <scene name='Journal:JBSD:38/Cv/3'>IGF receptor </scene> (IGF-IR, PDB ID: [[3i81]], <font color='darkmagenta'><b>colored in darkmagenta</b></font>) activation is critical for IGF-I to elicit desirable cognitive functions. Traditional Chinese medicine (TCM) ligands <scene name='Journal:JBSD:38/Cv/2'>3-(2-carboxyphenyl)-4(3H)-quinazolinone</scene> (orgin: ''Isatisin digotica'', <span style="color:lime;background-color:black;font-weight:bold;">colored in green</span>), <scene name='Journal:JBSD:38/Cv/4'>(+)-N-methyllaurotetanine</scene> (origin: ''Lindera aggregate'', <span style="color:deeppink;background-color:black;font-weight:bold;">colored in deeppink</span>), and <scene name='Journal:JBSD:38/Cv/5'>(+)-1(R)-Coclaurine</scene> (origin: ''Nelumbonucifera Gaertn'', <span style="color:salmon;background-color:black;font-weight:bold;">colored in salmon</span>) showed high binding affinity towards IGF-IR at the binding site defined by the control in PDB ID: [[3i81]]. Molecular dynamics simulation revealed that the TCM ligands were secured at the opening of the IGF-IR binding site for the duration of the MD. <scene name='Journal:JBSD:38/Cv/7'>3-(2-carboxyphenyl)-4(3H)-quinazolinone</scene> was stabilized by <scene name='Journal:JBSD:38/Cv/8'>Asp1056</scene>, <scene name='Journal:JBSD:38/Cv/9'>(+)-N-methyllaurotetanine</scene> was stabilized by <scene name='Journal:JBSD:38/Cv/10'>Leu975 and Asp1056</scene>, and <scene name='Journal:JBSD:38/Cv/11'>(+)-1(R)-Coclaurine</scene> was stabilized by <scene name='Journal:JBSD:38/Cv/12'>Leu975 and Gly1055</scene> (<span style="color:yellow;background-color:black;font-weight:bold;">key residues are colored in yellow</span>). Four different quantitative-structure activity relationship models consistently predicted bioactivity of the TCM ligands towards IGF-IR. In summary, the TCM candidates exhibit drug-like potential in both structural-based and ligand-based properties and may have potential for further applications in enhancing cognition.
+</StructureSection>
+__NOTOC__
-===3D structures of insulin-like growth factor receptor===
+==3D structures of insulin-like growth factor receptor==
 Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+{{#tree:id=OrganizedByTopic|openlevels=0|
-==IGFR I==
+*IGFR I
-[[1igr]] – hIGFR I domains 1-3 – human<BR />
+**[[1igr]] – hIGFR I domains 1-3 31-492– human<BR />
-[[1jqh]], [[1p4o]] - hIGFR I kinase domain (mutant) <BR />
+**[[1jqh]], [[1p4o]] - hIGFR I kinase domain (mutant) 983-1286<BR />
-[[1m7n]] - hIGFR I kinase domain<BR />
+**[[1m7n]] - hIGFR I kinase domain<BR />
-[[1k3a]] -  hIGFR I kinase domain + insulin receptor substrate peptide<BR />
+**[[1k3a]] -  hIGFR I kinase domain + insulin receptor substrate peptide<BR />
-[[2oj9]], [[2zm3]], [[3d94]], [[3f5p]], [[3i81]], [[3lvp]], [[3nw5]], [[3nw6]], [[3nw7]], [[3lw0]], [[3qqu]], [[3o23]] - hIGFR I kinase domain + inhibitor<BR />
+**[[2oj9]], [[2zm3]], [[3d94]], [[3f5p]], [[3i81]], [[3lvp]], [[3nw5]], [[3nw6]], [[3nw7]], [[3lw0]], [[3qqu]], [[3o23]], [[4d2r]], [[5fxq]], [[5fxr]], [[5fxs]], [[5hzn]] - hIGFR I kinase domain + inhibitor<BR />
+**[[5u8r]] - hIGFR I (mutant) + antibody<BR />
+**[[5u8q]] - hIGFR I (mutant) + IGFI + antibody<BR />
+**[[6pyh]] - hIGFR I + IGFI – Cryo EM<BR />
+**[[6vwg]], [[6vwh]], [[6vwi]], [[6vwj]] - hIGFR I + IGFII – Cryo EM<BR />
+**[[7s8v]] - hIGFR I + insulin receptor – Cryo EM<BR />
+**[[7s0q]] - hIGFR I + insulin receptor + IGF I – Cryo EM<BR />
-==IGFR II==
+*IGFR II
-[[1gqb]] - hIGFR II<BR />
+**[[1gqb]] - hIGFR II<BR />
-[[2kva]] - hIGFR II domain 5 – NMR<BR />
+**[[2kva]] - hIGFR II domain 5 – NMR<BR />
-[[2cnj]] - hIGFR II domain 11 - NMR<BR />
+**[[2cnj]] - hIGFR II domain 11 - NMR<BR />
-[[2l2a]] - hIGFR II domains 11 (mutant) - NMR<BR />
+**[[2l2a]], [[2m68]], [[2m6t]] - hIGFR II domains 11 (mutant) - NMR<BR />
-[[2kvb]] - hIGFR II domain 5 + inhibitor – NMR<BR />
+**[[2kvb]] - hIGFR II domain 5 + inhibitor – NMR<BR />
-[[2v5n]] - hIGFR II domains 11-12<BR />
+**[[2v5n]] - hIGFR II domains 11-12<BR />
-[[2v5o]] - hIGFR II domains 11-14<BR />
+**[[2v5o]] - hIGFR II domains 11-14<BR />
-[[2v5p]] - hIGFR II domains 11-13 + IGF II<BR />
+**[[2v5p]] - hIGFR II domains 11-13 + IGF II<BR />
-[[2l29]] - hIGFR II domain 11 + IGF II - NMR<BR />
+**[[2l29]] - hIGFR II domain 11 + IGF II - NMR<BR />
-[[1gp0]], [[1gp3]], [[1e6f]] - hIGFR II IGF II-binding domain<br />
+**[[1gp0]], [[1gp3]], [[1e6f]] - hIGFR II IGF II-binding domain<br />
-[[1q25]] - bIGFR II domains 1-3 – bovine<BR />
+**[[1q25]] - bIGFR II domains 1-3 – bovine<BR />
-[[1syo]], [[1sz0]] - bIGFR II domains 1-3 + mannose-6-phosphate<BR />
+**[[1syo]], [[1sz0]] - bIGFR II domains 1-3 + mannose-6-phosphate<BR />
+**[[2lla]] - IGFR II domain 11 – short-beaked echidna - NMR<BR />
+**[[2l2g]] - IGFR II domain 11 – opossum - NMR<BR />
+}}
+== References ==
+<references/>
 [[Category:Topic Page]]