Specificity of TGF-β1 signal designated by LRRC33 and integrin α_Vβ₈.

ABSTRACT: Myeloid lineage cells present the latent form of transforming growth factor-β1 (L-TGF-β1) to the membrane using an anchor protein LRRC33. Integrin α_Vβ₈ activates extracellular L-TGF-β1 to trigger the downstream signaling functions. However, the mechanism designating the specificity of TGF-β1 presentation and activation remains incompletely understood. Here, we report cryo-EM structures of human L-TGF-β1/LRRC33 and integrin α_Vβ₈/L-TGF-β1 complexes. Combined with biochemical and cell-based analyses, we demonstrate that LRRC33 only presents L-TGF-β1 but not the -β2 or -β3 isoforms due to difference of key residues on the growth factor domains. Moreover, we reveal a 2:2 binding mode of integrin α_Vβ₈ and L-TGF-β1, which shows hig

SUBMITTER: Duan Z 

PROVIDER: S-EPMC9411592 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature