|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2dsp' size='340' side='right'caption='[[2dsp]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='2dsp' size='340' side='right'caption='[[2dsp]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2dsp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DSP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2dsp]] 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=2DSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DSP FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1wqj|1wqj]], [[2dsq|2dsq]], [[2dsr|2dsr]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</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=2dsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dsp OCA], [https://pdbe.org/2dsp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dsp RCSB], [https://www.ebi.ac.uk/pdbsum/2dsp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dsp ProSAT]</span></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=2dsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dsp OCA], [https://pdbe.org/2dsp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dsp RCSB], [https://www.ebi.ac.uk/pdbsum/2dsp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dsp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == 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. | |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/IBP4_HUMAN IBP4_HUMAN]] IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. [[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/IBP4_HUMAN IBP4_HUMAN] IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 39: |
Line 37: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Holak, T A]] | + | [[Category: Holak TA]] |
| - | [[Category: Huber, R]] | + | [[Category: Huber R]] |
| - | [[Category: Popowicz, G M]] | + | [[Category: Popowicz GM]] |
| - | [[Category: Sitar, T]] | + | [[Category: Sitar T]] |
| - | [[Category: Siwanowicz, I]] | + | [[Category: Siwanowicz I]] |
| - | [[Category: Igf]]
| + | |
| - | [[Category: Igfbp]]
| + | |
| - | [[Category: Insulin]]
| + | |
| - | [[Category: Protein binding-hormone-growth factor complex]]
| + | |
| Structural highlights
Function
IBP4_HUMAN IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.
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
Insulin-like growth factor-binding proteins (IGFBPs) control bioavailability, activity, and distribution of insulin-like growth factor (IGF)1 and -2 through high-affinity IGFBP/IGF complexes. IGF-binding sites are found on N- and C-terminal fragments of IGFBPs, the two conserved domains of IGFBPs. The relative contributions of these domains to IGFBP/IGF complexation has been difficult to analyze, in part, because of the lack of appropriate three-dimensional structures. To analyze the effects of N- and C-terminal domain interactions, we determined several x-ray structures: first, of a ternary complex of N- and C-terminal domain fragments of IGFBP4 and IGF1 and second, of a "hybrid" ternary complex using the C-terminal domain fragment of IGFBP1 instead of IGFBP4. We also solved the binary complex of the N-terminal domains of IGFBP4 and IGF1, again to analyze C- and N-terminal domain interactions by comparison with the ternary complexes. The structures reveal the mechanisms of IGF signaling regulation via IGFBP binding. This finding supports research into the design of IGFBP variants as therapeutic IGF inhibitors for diseases of IGF disregulation. In IGFBP4, residues 1-38 form a rigid disulphide bond ladder-like structure, and the first five N-terminal residues bind to IGF and partially mask IGF residues responsible for the type 1 IGF receptor binding. A high-affinity IGF1-binding site is located in a globular structure between residues 39 and 82. Although the C-terminal domains do not form stable binary complexes with either IGF1 or the N-terminal domain of IGFBP4, in the ternary complex, the C-terminal domain contacts both and contributes to blocking of the IGF1 receptor-binding region of IGF1.
Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins.,Sitar T, Popowicz GM, Siwanowicz I, Huber R, Holak TA Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13028-33. Epub 2006 Aug 21. PMID:16924115[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sitar T, Popowicz GM, Siwanowicz I, Huber R, Holak TA. Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins. Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13028-33. Epub 2006 Aug 21. PMID:16924115
|
