6UJB
Integrin alpha-v beta-8 in complex with the Fabs C6D4 and 11D12v2
Summary for 6UJB
| Entry DOI | 10.2210/pdb6ujb/pdb |
| EMDB information | 20794 20795 20796 20797 20798 20799 20800 20801 20802 |
| Descriptor | Integrin alpha-V, Integrin beta-8, C6D4 heavy chain Fab, ... (9 entities in total) |
| Functional Keywords | glycoprotein, adhesion, signaling, signaling protein-immune system complex, signaling protein/immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 244675.14 |
| Authors | Campbell, M.G.,Cormier, A.,Cheng, Y.,Nishimura, S.L. (deposition date: 2019-10-02, release date: 2020-02-05, Last modification date: 2024-11-06) |
| Primary citation | Campbell, M.G.,Cormier, A.,Ito, S.,Seed, R.I.,Bondesson, A.J.,Lou, J.,Marks, J.D.,Baron, J.L.,Cheng, Y.,Nishimura, S.L. Cryo-EM Reveals Integrin-Mediated TGF-beta Activation without Release from Latent TGF-beta. Cell, 180:490-, 2020 Cited by PubMed Abstract: Integrin αvβ8 binds with exquisite specificity to latent transforming growth factor-β (L-TGF-β). This binding is essential for activating L-TGF-β presented by a variety of cell types. Inhibiting αvβ8-mediated TGF-β 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 αvβ8 ectodomain and its intact natural ligand, L-TGF-β, as well as two different inhibitory antibody fragments to understand the structural underpinnings of αvβ8 binding specificity and TGF-β activation. Our studies reveal a mechanism of TGF-β activation where mature TGF-β signals within the confines of L-TGF-β and the release and diffusion of TGF-β are not required. The structural details of this mechanism provide a rational basis for therapeutic strategies to inhibit αvβ8-mediated L-TGF-β activation. PubMed: 31955848DOI: 10.1016/j.cell.2019.12.030 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.51 Å) |
Structure validation
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