6ujb: Difference between revisions

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<StructureSection load='6ujb' size='340' side='right'caption='[[6ujb]], [[Resolution|resolution]] 3.51&Aring;' scene=''>
<StructureSection load='6ujb' size='340' side='right'caption='[[6ujb]], [[Resolution|resolution]] 3.51&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ujb]] is a 4 chain structure. 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UJB FirstGlance]. <br>
<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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UJB 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>
</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='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://oca.weizmann.ac.il/oca-docs/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>
<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=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>
</table>
</table>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Campbell, M G]]
[[Category: Campbell, M G]]
[[Category: Cheng, Y]]
[[Category: Cheng, Y]]

Revision as of 10:41, 19 February 2020

Integrin alpha-v beta-8 in complex with the Fabs C6D4 and 11D12v2Integrin alpha-v beta-8 in complex with the Fabs C6D4 and 11D12v2

Structural highlights

6ujb is a 4 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , ,
Gene:ITGAV, MSK8, VNRA, VTNR (HUMAN), ITGB8 (HUMAN)
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. [ITB8_HUMAN] Integrin alpha-V/beta-8 is a receptor for fibronectin.

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[1]

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

References

  1. Campbell MG, Cormier A, Ito S, Seed RI, Bondesson AJ, Lou J, Marks JD, Baron JL, Cheng Y, Nishimura SL. Cryo-EM Reveals Integrin-Mediated TGF-beta Activation without Release from Latent TGF-beta. Cell. 2020 Jan 13. pii: S0092-8674(19)31392-3. doi: 10.1016/j.cell.2019.12.030. PMID:31955848 doi:http://dx.doi.org/10.1016/j.cell.2019.12.030

6ujb, resolution 3.51Å

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