View source for 6ujb


==Integrin alpha-v beta-8 in complex with the Fabs C6D4 and 11D12v2==
<SX load='6ujb' size='340' side='right' viewer='molstar' caption='[[6ujb]], [[Resolution|resolution]] 3.51&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ujb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UJB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UJB 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=MG:MAGNESIUM+ION'>MG</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, VTNR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB8 ([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=6ujb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ujb OCA], [http://pdbe.org/6ujb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ujb RCSB], [http://www.ebi.ac.uk/pdbsum/6ujb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ujb ProSAT]</span></td></tr>
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== 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. 
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
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[[Category: Human]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[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]]