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| | <StructureSection load='5ffo' size='340' side='right'caption='[[5ffo]], [[Resolution|resolution]] 3.49Å' scene=''> | | <StructureSection load='5ffo' size='340' side='right'caption='[[5ffo]], [[Resolution|resolution]] 3.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ffo]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FFO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FFO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ffo]] is a 8 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=5FFO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FFO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 3.49Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ffg|5ffg]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ITGAV, MSK8, VNRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TGFB1, TGFB ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5ffo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ffo OCA], [https://pdbe.org/5ffo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ffo RCSB], [https://www.ebi.ac.uk/pdbsum/5ffo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ffo ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ffo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ffo OCA], [http://pdbe.org/5ffo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ffo RCSB], [http://www.ebi.ac.uk/pdbsum/5ffo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ffo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/TGFB1_HUMAN TGFB1_HUMAN]] Defects in TGFB1 are the cause of Camurati-Engelmann disease (CE) [MIM:[http://omim.org/entry/131300 131300]]; also known as progressive diaphyseal dysplasia 1 (DPD1). CE is an autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. The disease typically presents in early childhood with pain, muscular weakness and waddling gait, and in some cases other features such as exophthalmos, facial paralysis, hearing difficulties and loss of vision.<ref>PMID:10973241</ref> <ref>PMID:11062463</ref> <ref>PMID:12493741</ref> <ref>PMID:12843182</ref> <ref>PMID:15103729</ref> [[http://www.uniprot.org/uniprot/ITB6_HUMAN ITB6_HUMAN]] Hypocalcified amelogenesis imperfecta;Hypoplastic amelogenesis imperfecta. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ITAV_HUMAN ITAV_HUMAN]] The alpha-V integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. [[http://www.uniprot.org/uniprot/TGFB1_HUMAN TGFB1_HUMAN]] Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. [[http://www.uniprot.org/uniprot/ITB6_HUMAN ITB6_HUMAN]] Integrin alpha-V/beta-6 is a receptor for fibronectin and cytotactin. It recognizes the sequence R-G-D in its ligands. Internalisation of integrin alpha-V/beta-6 via clathrin-mediated endocytosis promotes carcinoma cell invasion.<ref>PMID:17545607</ref> | + | [https://www.uniprot.org/uniprot/ITAV_HUMAN ITAV_HUMAN] The alpha-V integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dong, X]] | + | [[Category: Dong X]] |
| - | [[Category: Springer, T A]] | + | [[Category: Springer TA]] |
| - | [[Category: Zhao, B]] | + | [[Category: Zhao B]] |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Integrin]]
| + | |
| - | [[Category: Tgf-beta]]
| + | |
| Structural highlights
5ffo is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 3.49Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ITAV_HUMAN The alpha-V integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
Publication Abstract from PubMed
Integrins are adhesion receptors that transmit force across the plasma membrane between extracellular ligands and the actin cytoskeleton. In activation of the transforming growth factor-beta1 precursor (pro-TGF-beta1), integrins bind to the prodomain, apply force, and release the TGF-beta growth factor. However, we know little about how integrins bind macromolecular ligands in the extracellular matrix or transmit force to them. Here we show how integrin alphaVbeta6 binds pro-TGF-beta1 in an orientation biologically relevant for force-dependent release of TGF-beta from latency. The conformation of the prodomain integrin-binding motif differs in the presence and absence of integrin binding; differences extend well outside the interface and illustrate how integrins can remodel extracellular matrix. Remodelled residues outside the interface stabilize the integrin-bound conformation, adopt a conformation similar to earlier-evolving family members, and show how macromolecular components outside the binding motif contribute to integrin recognition. Regions in and outside the highly interdigitated interface stabilize a specific integrin/pro-TGF-beta orientation that defines the pathway through these macromolecules which actin-cytoskeleton-generated tensile force takes when applied through the integrin beta-subunit. Simulations of force-dependent activation of TGF-beta demonstrate evolutionary specializations for force application through the TGF-beta prodomain and through the beta- and not alpha-subunit of the integrin.
Force interacts with macromolecular structure in activation of TGF-beta.,Dong X, Zhao B, Iacob RE, Zhu J, Koksal AC, Lu C, Engen JR, Springer TA Nature. 2017 Feb 2;542(7639):55-59. doi: 10.1038/nature21035. Epub 2017 Jan 25. PMID:28117447[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dong X, Zhao B, Iacob RE, Zhu J, Koksal AC, Lu C, Engen JR, Springer TA. Force interacts with macromolecular structure in activation of TGF-beta. Nature. 2017 Feb 2;542(7639):55-59. doi: 10.1038/nature21035. Epub 2017 Jan 25. PMID:28117447 doi:http://dx.doi.org/10.1038/nature21035
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