6nsv

Crystal structure of the human CHIP TPR domain in complex with a 5mer acetylated optimized peptide

spinqualitylabelsall models 6nsv, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6nsv is a 4 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 1.305Å Ligands: 1PE, ACE, CL, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Protein-protein interactions between E3 ubiquitin ligases and protein termini help shape the proteome. These interactions are sensitive to proteolysis, which alters the ensemble of cellular N and C termini. Here we describe a mechanism wherein caspase activity reveals latent C termini that are then recognized by the E3 ubiquitin ligase CHIP. Using expanded knowledge of CHIP's binding specificity, we predicted hundreds of putative interactions arising from caspase activity. Subsequent validation experiments confirmed that CHIP binds the latent C termini at tau(D421) and caspase-6(D179). CHIP binding to tau(D421), but not tau(FL), promoted its ubiquitination, while binding to caspase-6(D179) mediated ubiquitin-independent inhibition. Given that caspase activity generates tau(D421) in Alzheimer's disease (AD), these results suggested a concise model for CHIP regulation of tau homeostasis. Indeed, we find that loss of CHIP expression in AD coincides with the accumulation of tau(D421) and caspase-6(D179). These results illustrate an unanticipated link between caspases and protein homeostasis. Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases.,Ravalin M, Theofilas P, Basu K, Opoku-Nsiah KA, Assimon VA, Medina-Cleghorn D, Chen YF, Bohn MF, Arkin M, Grinberg LT, Craik CS, Gestwicki JE Nat Chem Biol. 2019 Aug;15(8):786-794. doi: 10.1038/s41589-019-0322-6. Epub 2019 , Jul 18. PMID:31320752 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ubiquitin protein ligase 3D structures

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