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6UJA

Integrin alpha-v beta-8 in complex with pro-TGF-beta1

Summary for 6UJA
Entry DOI10.2210/pdb6uja/pdb
EMDB information20794 20795 20796 20797 20798 20799 20800 20801 20802 21125
DescriptorIntegrin alpha-V, Integrin beta-8, Transforming growth factor beta-1 proprotein, ... (8 entities in total)
Functional Keywordsglycoprotein, adhesion, signaling, signaling protein
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains3
Total formula weight239183.35
Authors
Campbell, M.G.,Cormier, A.,Cheng, Y.,Nishimura, S.L. (deposition date: 2019-10-02, release date: 2020-02-05, Last modification date: 2024-10-16)
Primary citationCampbell, 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: 31955848
DOI: 10.1016/j.cell.2019.12.030
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.3 Å)
Structure validation

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건을2024-11-06부터공개중

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