7y1t

Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2

Structural highlights 7y1t is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , , 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. Publication Abstract from PubMed Myeloid lineage cells present the latent form of transforming growth factor-beta1 (L-TGF-beta1) to the membrane using an anchor protein LRRC33. Integrin alphaVbeta8 activates extracellular L-TGF-beta1 to trigger the downstream signaling functions. However, the mechanism designating the specificity of TGF-beta1 presentation and activation remains incompletely understood. Here, we report cryo-EM structures of human L-TGF-beta1/LRRC33 and integrin alphaVbeta8/L-TGF-beta1 complexes. Combined with biochemical and cell-based analyses, we demonstrate that LRRC33 only presents L-TGF-beta1 but not the -beta2 or -beta3 isoforms due to difference of key residues on the growth factor domains. Moreover, we reveal a 2:2 binding mode of integrin alphaVbeta8 and L-TGF-beta1, which shows higher avidity and more efficient L-TGF-beta1 activation than previously reported 1:2 binding mode. We also uncover that the disulfide-linked loop of the integrin subunit beta8 determines its exquisite affinity to L-TGF-beta1. Together, our findings provide important insights into the specificity of TGF-beta1 signaling achieved by LRRC33 and integrin alphaVbeta8. Specificity of TGF-beta1 signal designated by LRRC33 and integrin alphaVbeta8.,Duan Z, Lin X, Wang L, Zhen Q, Jiang Y, Chen C, Yang J, Lee CH, Qin Y, Li Y, Zhao B, Wang J, Zhang Z Nat Commun. 2022 Aug 25;13(1):4988. doi: 10.1038/s41467-022-32655-9. PMID:36008481 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 7y1t, resolution 3.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image