8fxv

Crystal structure of human proTGF-beta2 in complex with Nb18

spinqualitylabelsall models 8fxv, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fxv is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Activation of latent transforming growth factor (TGF)-beta2 is incompletely understood. Unlike TGF-beta1 and beta3, the TGF-beta2 prodomain lacks a seven-residue RGDLXX (L/I) integrin-recognition motif and is thought not to be activated by integrins. Here, we report the surprising finding that TGF-beta2 contains a related but divergent 13-residue integrin-recognition motif (YTSGDQKTIKSTR) that specializes it for activation by integrin alphaVbeta6 but not alphaVbeta8. Both classes of motifs compete for the same binding site in alphaVbeta6. Multiple changes in the longer motif underlie its specificity. ProTGF-beta2 structures define interesting differences from proTGF-beta1 and the structural context for activation by alphaVbeta6. Some integrin-independent activation is also seen for proTGF-beta2 and even more so for proTGF-beta3. Our findings have important implications for therapeutics to alphaVbeta6 in clinical trials for fibrosis, in which inhibition of TGF-beta2 activation has not been anticipated. A specialized integrin-binding motif enables proTGF-beta2 activation by integrin alphaVbeta6 but not alphaVbeta8.,Le VQ, Zhao B, Ramesh S, Toohey C, DeCosta A, Mintseris J, Liu X, Gygi S, Springer TA Proc Natl Acad Sci U S A. 2023 Jun 13;120(24):e2304874120. doi: , 10.1073/pnas.2304874120. Epub 2023 Jun 6. PMID:37279271 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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