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5ffo

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Revision as of 07:17, 6 May 2020

Integrin alpha V beta 6 in complex with pro-TGF-beta

Structural highlights

5ffo is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	5ffg
Gene:	ITGAV, MSK8, VNRA (HUMAN), ITGB6 (HUMAN), TGFB1, TGFB (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TGFB1_HUMAN] Defects in TGFB1 are the cause of Camurati-Engelmann disease (CE) [MIM: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.^[1] ^[2] ^[3] ^[4] ^[5] [ITB6_HUMAN] Hypocalcified amelogenesis imperfecta;Hypoplastic amelogenesis imperfecta.

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. [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. [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.^[6]

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kinoshita A, Saito T, Tomita H, Makita Y, Yoshida K, Ghadami M, Yamada K, Kondo S, Ikegawa S, Nishimura G, Fukushima Y, Nakagomi T, Saito H, Sugimoto T, Kamegaya M, Hisa K, Murray JC, Taniguchi N, Niikawa N, Yoshiura K. Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease. Nat Genet. 2000 Sep;26(1):19-20. PMID:10973241 doi:10.1038/79128
↑ Janssens K, Gershoni-Baruch R, Guanabens N, Migone N, Ralston S, Bonduelle M, Lissens W, Van Maldergem L, Vanhoenacker F, Verbruggen L, Van Hul W. Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease. Nat Genet. 2000 Nov;26(3):273-5. PMID:11062463 doi:10.1038/81563
↑ Janssens K, ten Dijke P, Ralston SH, Bergmann C, Van Hul W. Transforming growth factor-beta 1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein. J Biol Chem. 2003 Feb 28;278(9):7718-24. Epub 2002 Dec 18. PMID:12493741 doi:10.1074/jbc.M208857200
↑ McGowan NW, MacPherson H, Janssens K, Van Hul W, Frith JC, Fraser WD, Ralston SH, Helfrich MH. A mutation affecting the latency-associated peptide of TGFbeta1 in Camurati-Engelmann disease enhances osteoclast formation in vitro. J Clin Endocrinol Metab. 2003 Jul;88(7):3321-6. PMID:12843182
↑ Kinoshita A, Fukumaki Y, Shirahama S, Miyahara A, Nishimura G, Haga N, Namba A, Ueda H, Hayashi H, Ikegawa S, Seidel J, Niikawa N, Yoshiura K. TGFB1 mutations in four new families with Camurati-Engelmann disease: confirmation of independently arising LAP-domain-specific mutations. Am J Med Genet A. 2004 May 15;127A(1):104-7. PMID:15103729 doi:10.1002/ajmg.a.20671
↑ Ramsay AG, Keppler MD, Jazayeri M, Thomas GJ, Parsons M, Violette S, Weinreb P, Hart IR, Marshall JF. HS1-associated protein X-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin alphavbeta6. Cancer Res. 2007 Jun 1;67(11):5275-84. PMID:17545607 doi:http://dx.doi.org/10.1158/0008-5472.CAN-07-0318
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ffo"

@@ Line 1: / Line 1: @@
 ==Integrin alpha V beta 6 in complex with pro-TGF-beta==
-<StructureSection load='5ffo' size='340' side='right' caption='[[5ffo]], [[Resolution|resolution]] 3.49&Aring;' scene=''>
+<StructureSection load='5ffo' size='340' side='right'caption='[[5ffo]], [[Resolution|resolution]] 3.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ffo]] is a 8 chain structure. 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FFO FirstGlance]. <br>
+<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>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ffg|5ffg]]</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=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>
+<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'>[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>
 == Disease ==
@@ Line 21: / Line 22: @@
 </div>
 <div class="pdbe-citations 5ffo" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Integrin 3D structures|Integrin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Dong, X]]
 [[Category: Springer, T A]]

5ffo

From Proteopedia

Revision as of 07:17, 6 May 2020

Integrin alpha V beta 6 in complex with pro-TGF-beta

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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