6rva
From Proteopedia
(Difference between revisions)
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<StructureSection load='6rva' size='340' side='right'caption='[[6rva]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | <StructureSection load='6rva' size='340' side='right'caption='[[6rva]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6rva]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RVA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RVA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rva]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RVA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RVA FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rva FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rva OCA], [http://pdbe.org/6rva PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rva RCSB], [http://www.ebi.ac.uk/pdbsum/6rva PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rva ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGF1, IBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rva FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rva OCA], [http://pdbe.org/6rva PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rva RCSB], [http://www.ebi.ac.uk/pdbsum/6rva PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rva ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN]] The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in rat bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake.<ref>PMID:21076856</ref> | [[http://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN]] The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in rat bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake.<ref>PMID:21076856</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Information on how insulin and insulin-like growth factors 1 and 2 (IGF-1 and -2) activate insulin receptors (IR-A and -B) and the IGF-1 receptor (IGF-1R) is crucial for understanding the difference in the biological activities of these peptide hormones. Cryo-EM studies have revealed that insulin uses its binding sites 1 and 2 to interact with IR-A and have identified several critical residues in binding site 2. However, mutagenesis studies suggest that IleA10, SerA12, LeuA13, and GluA17 also belong to insulin's site 2. Here, to resolve this discrepancy, we mutated these insulin residues and the equivalent residues in IGFs. Our findings revealed that equivalent mutations in the hormones can result in differential biological effects and that these effects can be receptor-specific. We noted that the insulin positions A10 and A17 are important for its binding to IR-A and IR-B and IGF-1R and that A13 is important only for IR-A and IR-B binding. The IGF-1/IGF-2 positions 51/50 and 54/53 did not appear to play critical roles in receptor binding, but mutations at IGF-1 position 58 and IGF-2 position 57 affected the binding. We propose that IGF-1 Glu58 interacts with IGF-1R Arg704 and belongs to IGF-1 site 1, a finding supported by the NMR structure of the less active Asp58-IGF-1 variant. Computational analyses indicated that the aforementioned mutations can affect internal insulin dynamics and inhibit adoption of a receptor-bound conformation, important for binding to receptor site 1. We provide a molecular model and alternative hypotheses for how the mutated insulin residues affect activity. | ||
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| + | Mutations at hypothetical binding site 2 in insulin and insulin-like growth factors 1 and 2 result in receptor- and hormone-specific responses.,Machackova K, Mlcochova K, Potalitsyn P, Hankova K, Socha O, Budesinsky M, Muzdalo A, Lepsik M, Cernekova M, Radosavljevic J, Fabry M, Mitrova K, Chrudinova M, Lin J, Yurenko Y, Hobza P, Selicharova I, Akova L, Jiracek J J Biol Chem. 2019 Sep 26. pii: RA119.010072. doi: 10.1074/jbc.RA119.010072. PMID:31558604<ref>PMID:31558604</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6rva" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Jiracek, J]] | [[Category: Jiracek, J]] | ||
Revision as of 06:25, 10 October 2019
STRUCTURE OF [ASP58]-IGF-I ANALOGUE
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Categories: Human | Large Structures | Jiracek, J | Socha, O | Zakova, L | Hormone | Igf-i analogue
