7y1t: Difference between revisions
New page: '''Unreleased structure''' The entry 7y1t is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2== | |||
<StructureSection load='7y1t' size='340' side='right'caption='[[7y1t]], [[Resolution|resolution]] 3.24Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7y1t]] is a 3 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=7Y1T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y1T 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=MN:MANGANESE+(II)+ION'>MN</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'>[https://proteopedia.org/fgij/fg.htm?mol=7y1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y1t OCA], [https://pdbe.org/7y1t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y1t RCSB], [https://www.ebi.ac.uk/pdbsum/7y1t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y1t ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[https://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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Myeloid lineage cells present the latent form of transforming growth factor-beta1 (L-TGF-beta1) to the membrane using an anchor protein LRRC33. Integrin alphaVbeta8 activates extracellular L-TGF-beta1 to trigger the downstream signaling functions. However, the mechanism designating the specificity of TGF-beta1 presentation and activation remains incompletely understood. Here, we report cryo-EM structures of human L-TGF-beta1/LRRC33 and integrin alphaVbeta8/L-TGF-beta1 complexes. Combined with biochemical and cell-based analyses, we demonstrate that LRRC33 only presents L-TGF-beta1 but not the -beta2 or -beta3 isoforms due to difference of key residues on the growth factor domains. Moreover, we reveal a 2:2 binding mode of integrin alphaVbeta8 and L-TGF-beta1, which shows higher avidity and more efficient L-TGF-beta1 activation than previously reported 1:2 binding mode. We also uncover that the disulfide-linked loop of the integrin subunit beta8 determines its exquisite affinity to L-TGF-beta1. Together, our findings provide important insights into the specificity of TGF-beta1 signaling achieved by LRRC33 and integrin alphaVbeta8. | |||
Specificity of TGF-beta1 signal designated by LRRC33 and integrin alphaVbeta8.,Duan Z, Lin X, Wang L, Zhen Q, Jiang Y, Chen C, Yang J, Lee CH, Qin Y, Li Y, Zhao B, Wang J, Zhang Z Nat Commun. 2022 Aug 25;13(1):4988. doi: 10.1038/s41467-022-32655-9. PMID:36008481<ref>PMID:36008481</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7y1t" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Duan Z]] | |||
[[Category: Zhang Z]] | |||
Latest revision as of 22:00, 7 September 2022
Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2
Structural highlights
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. Publication Abstract from PubMedMyeloid lineage cells present the latent form of transforming growth factor-beta1 (L-TGF-beta1) to the membrane using an anchor protein LRRC33. Integrin alphaVbeta8 activates extracellular L-TGF-beta1 to trigger the downstream signaling functions. However, the mechanism designating the specificity of TGF-beta1 presentation and activation remains incompletely understood. Here, we report cryo-EM structures of human L-TGF-beta1/LRRC33 and integrin alphaVbeta8/L-TGF-beta1 complexes. Combined with biochemical and cell-based analyses, we demonstrate that LRRC33 only presents L-TGF-beta1 but not the -beta2 or -beta3 isoforms due to difference of key residues on the growth factor domains. Moreover, we reveal a 2:2 binding mode of integrin alphaVbeta8 and L-TGF-beta1, which shows higher avidity and more efficient L-TGF-beta1 activation than previously reported 1:2 binding mode. We also uncover that the disulfide-linked loop of the integrin subunit beta8 determines its exquisite affinity to L-TGF-beta1. Together, our findings provide important insights into the specificity of TGF-beta1 signaling achieved by LRRC33 and integrin alphaVbeta8. Specificity of TGF-beta1 signal designated by LRRC33 and integrin alphaVbeta8.,Duan Z, Lin X, Wang L, Zhen Q, Jiang Y, Chen C, Yang J, Lee CH, Qin Y, Li Y, Zhao B, Wang J, Zhang Z Nat Commun. 2022 Aug 25;13(1):4988. doi: 10.1038/s41467-022-32655-9. PMID:36008481[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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