6ujc
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Integrin alpha-v beta-8 in complex with the Fabs C6-RGD3 and 11D12v2== | |
| + | <StructureSection load='6ujc' size='340' side='right'caption='[[6ujc]], [[Resolution|resolution]] 3.56Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6ujc]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UJC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UJC 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></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=6ujc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ujc OCA], [http://pdbe.org/6ujc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ujc RCSB], [http://www.ebi.ac.uk/pdbsum/6ujc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ujc ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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/ITB8_HUMAN ITB8_HUMAN]] Integrin alpha-V/beta-8 is a receptor for fibronectin. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Integrin alphavbeta8 binds with exquisite specificity to latent transforming growth factor-beta (L-TGF-beta). This binding is essential for activating L-TGF-beta presented by a variety of cell types. Inhibiting alphavbeta8-mediated TGF-beta activation blocks immunosuppressive regulatory T cell differentiation, which is a potential therapeutic strategy in cancer. Using cryo-electron microscopy, structure-guided mutagenesis, and cell-based assays, we reveal the binding interactions between the entire alphavbeta8 ectodomain and its intact natural ligand, L-TGF-beta, as well as two different inhibitory antibody fragments to understand the structural underpinnings of alphavbeta8 binding specificity and TGF-beta activation. Our studies reveal a mechanism of TGF-beta activation where mature TGF-beta signals within the confines of L-TGF-beta and the release and diffusion of TGF-beta are not required. The structural details of this mechanism provide a rational basis for therapeutic strategies to inhibit alphavbeta8-mediated L-TGF-beta activation. | ||
| - | + | Cryo-EM Reveals Integrin-Mediated TGF-beta Activation without Release from Latent TGF-beta.,Campbell MG, Cormier A, Ito S, Seed RI, Bondesson AJ, Lou J, Marks JD, Baron JL, Cheng Y, Nishimura SL Cell. 2020 Jan 13. pii: S0092-8674(19)31392-3. doi: 10.1016/j.cell.2019.12.030. PMID:31955848<ref>PMID:31955848</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6ujc" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Campbell, M G]] | ||
| + | [[Category: Cheng, Y]] | ||
| + | [[Category: Cormier, A]] | ||
| + | [[Category: Nishimura, S L]] | ||
| + | [[Category: Adhesion]] | ||
| + | [[Category: Glycoprotein]] | ||
| + | [[Category: Signaling]] | ||
| + | [[Category: Signaling protein-immune system complex]] | ||
Revision as of 08:12, 5 February 2020
Integrin alpha-v beta-8 in complex with the Fabs C6-RGD3 and 11D12v2
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