7y1r
From Proteopedia
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== Function == | == Function == | ||
[[https://www.uniprot.org/uniprot/TGFB1_HUMAN TGFB1_HUMAN]] Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. | [[https://www.uniprot.org/uniprot/TGFB1_HUMAN TGFB1_HUMAN]] Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:36008481</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7y1r" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 19:00, 7 September 2022
Human L-TGF-beta1 in complex with the anchor protein LRRC33
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