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| | ==Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I== | | ==Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I== |
| - | <StructureSection load='3lri' size='340' side='right'caption='[[3lri]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='3lri' size='340' side='right'caption='[[3lri]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lri]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LRI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lri]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LRI FirstGlance]. <br> |
| - | </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=3lri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lri OCA], [https://pdbe.org/3lri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lri RCSB], [https://www.ebi.ac.uk/pdbsum/3lri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lri ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=3lri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lri OCA], [https://pdbe.org/3lri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lri RCSB], [https://www.ebi.ac.uk/pdbsum/3lri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lri ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN]] Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:[https://omim.org/entry/608747 608747]]. IGF1 deficiency is an autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation.
| + | [https://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN] Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:[https://omim.org/entry/608747 608747]. IGF1 deficiency is an autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation. |
| | == Function == | | == Function == |
| - | [[https://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>
| + | [https://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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Carver, J A]] | + | [[Category: Carver JA]] |
| - | [[Category: Francis, G L]] | + | [[Category: Francis GL]] |
| - | [[Category: Keniry, M A]] | + | [[Category: Keniry MA]] |
| - | [[Category: Laajoki, L G]] | + | [[Category: Laajoki LG]] |
| - | [[Category: Wallace, J C]] | + | [[Category: Wallace JC]] |
| - | [[Category: Distance geometry]]
| + | |
| - | [[Category: Growth factor]]
| + | |
| - | [[Category: Insulin-like growth factor-1]]
| + | |
| - | [[Category: Protein structure]]
| + | |
| Structural highlights
Disease
IGF1_HUMAN Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:608747. IGF1 deficiency is an autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation.
Function
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.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Long-[Arg(3)]insulin-like growth factor-I (IGF-I) is a potent analog of insulin-like growth factor-I that has been modified by a Glu(3) --> Arg mutation and a 13-amino acid extension appended to the N terminus. We have determined the solution structure of (15)N-labeled Long-[Arg(3)]-IGF-I using high resolution NMR and restrained molecular dynamics techniques to a precision of 0.82 +/- 0.28 A root mean square deviation for the backbone heavy atoms in the three alpha-helices and 3.5 +/- 0.9 A root mean square deviation for all backbone heavy atoms excluding the 8 N-terminal residues and the 8 C-terminal eight residues. Overall, the structure of the IGF-I domain is consistent with earlier studies of IGF-I with some minor changes remote from the N terminus. The major variations in the structure, compared with IGF-I, occur at the N terminus with a substantial reorientation of the N-terminal three residues of the IGF-I domain. These results are interpreted in terms of the lower binding affinity for insulin-like growth factor-binding proteins. The backbone dynamics of Long-[Arg(3)]IGF-I were investigated using (15)N nuclear spin relaxation and the heteronuclear nuclear Overhauser enhancement (NOE). There is a considerable degree of flexibility in Long-[Arg(3)]IGF-I, even in the alpha-helices, as indicated by an average ((1)H)(15)N NOE of 0.55 for the regions. The largest heteronuclear NOEs are observed in the helical regions, lower heteronuclear NOEs are observed in the C-domain loop separating helix 1 from helix 2, and negative heteronuclear NOEs are observed in the N-terminal extension and at the C terminus. Despite these data indicating conformational flexibility for the N-terminal extension, slow amide proton exchange was observed for some residues in this region, suggesting some transitory structure does exist, possibly a molten helix. A certain degree of flexibility may be necessary in all insulin-like growth factors to enable association with various receptors and binding proteins.
Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I.,Laajoki LG, Francis GL, Wallace JC, Carver JA, Keniry MA J Biol Chem. 2000 Apr 7;275(14):10009-15. PMID:10744677[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zoidis E, Ghirlanda-Keller C, Schmid C. Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I. Mol Cell Biochem. 2011 Feb;348(1-2):33-42. doi: 10.1007/s11010-010-0634-z. Epub, 2010 Nov 13. PMID:21076856 doi:10.1007/s11010-010-0634-z
- ↑ Laajoki LG, Francis GL, Wallace JC, Carver JA, Keniry MA. Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I. J Biol Chem. 2000 Apr 7;275(14):10009-15. PMID:10744677
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