Structural highlights
6ujc 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.
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| 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
- ↑ 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
