6EFK

Crystal structure of the human CHIP TPR domain in complex with a 5mer acetylated HSP70 peptide

6EFK の概要

• エントリーDOI: 10.2210/pdb6efk/pdb
• 分子名称: E3 ubiquitin-protein ligase CHIP, ACE-ILE-GLU-GLU-VAL-ASP, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: c-terminus of hsc70-interacting protein, heat shock protein 70, chip, hsp70, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 31726.92

構造登録者

Basu, K.,Ravalin, M.,Bohn, M.-F.,Craik, C.S.,Gestwicki, J.E. (登録日: 2018-08-16, 公開日: 2019-07-31, 最終更新日: 2024-11-13)

主引用文献

Ravalin, M.,Theofilas, P.,Basu, K.,Opoku-Nsiah, K.A.,Assimon, V.A.,Medina-Cleghorn, D.,Chen, Y.F.,Bohn, M.F.,Arkin, M.,Grinberg, L.T.,Craik, C.S.,Gestwicki, J.E.
Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases.
Nat.Chem.Biol., 15:786-794, 2019

PubMed Abstract: 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 and caspase-6. CHIP binding to tau, but not tau, promoted its ubiquitination, while binding to caspase-6 mediated ubiquitin-independent inhibition. Given that caspase activity generates tau 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 and caspase-6. These results illustrate an unanticipated link between caspases and protein homeostasis.

PubMed: 31320752
DOI: 10.1038/s41589-019-0322-6

実験手法

X-RAY DIFFRACTION (1.5 Å)