6ujc | pdb_00006ujc

Integrin alpha-v beta-8 in complex with the Fabs C6-RGD3 and 11D12v2

Loading... Status: waiting for Mol* initialization Structural highlights 6ujc is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.56Å Ligands: BMA, CA, MAN, MG, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Integrin 3D structures

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