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| | ==Crystal structure of alpha V beta 6 with peptide== | | ==Crystal structure of alpha V beta 6 with peptide== |
| - | <StructureSection load='4um9' size='340' side='right' caption='[[4um9]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4um9' size='340' side='right'caption='[[4um9]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4um9]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UM9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UM9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4um9]] is a 6 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=4UM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UM9 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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.5Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NHH:N-{4-[2-(DIAMINOMETHYLIDENE)HYDRAZONO]CYCLOHEXYLIDEN}AMINOMETHANEHYDRAZONAMIDE'>NHH</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4um8|4um8]]</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=4um9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4um9 OCA], [https://pdbe.org/4um9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4um9 RCSB], [https://www.ebi.ac.uk/pdbsum/4um9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4um9 ProSAT]</span></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=4um9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4um9 OCA], [http://pdbe.org/4um9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4um9 RCSB], [http://www.ebi.ac.uk/pdbsum/4um9 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ITB6_HUMAN ITB6_HUMAN]] Hypocalcified amelogenesis imperfecta;Hypoplastic amelogenesis imperfecta. | + | [https://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/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/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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Integrin|Integrin]] | + | *[[Integrin 3D structures|Integrin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dong, X]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Springer, T A]] | + | [[Category: Large Structures]] |
| - | [[Category: Cell surface receptor]] | + | [[Category: Dong X]] |
| - | [[Category: Immune system]] | + | [[Category: Springer TA]] |
| Structural highlights
4um9 is a 6 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 2.5Å |
| Ligands: | , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
ITB6_HUMAN Hypocalcified amelogenesis imperfecta;Hypoplastic amelogenesis imperfecta.
Function
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.[1]
Publication Abstract from PubMed
Eight integrin alpha-beta heterodimers recognize ligands with an Arg-Gly-Asp (RGD) motif. However, the structural mechanism by which integrins differentiate among extracellular proteins with RGD motifs is not understood. Here, crystal structures, mutations and peptide-affinity measurements show that alphaVbeta6 binds with high affinity to a RGDLXXL/I motif within the prodomains of TGF-beta1 and TGF-beta3. The LXXL/I motif forms an amphipathic alpha-helix that binds in a hydrophobic pocket in the beta6 subunit. Elucidation of the basis for ligand binding specificity by the integrin beta subunit reveals contributions by three different betaI-domain loops, which we designate specificity-determining loops (SDLs) 1, 2 and 3. Variation in a pair of single key residues in SDL1 and SDL3 correlates with the variation of the entire beta subunit in integrin evolution, thus suggesting a paradigmatic role in overall beta-subunit function.
Structural determinants of integrin beta-subunit specificity for latent TGF-beta,Dong X, Hudson NE, Lu C, Springer TA Nat Struct Mol Biol. 2014 Nov 10. doi: 10.1038/nsmb.2905. PMID:25383667[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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, Hudson NE, Lu C, Springer TA. Structural determinants of integrin beta-subunit specificity for latent TGF-beta Nat Struct Mol Biol. 2014 Nov 10. doi: 10.1038/nsmb.2905. PMID:25383667 doi:http://dx.doi.org/10.1038/nsmb.2905
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