8HAE

Cryo-EM structure of HACE1 dimer

8HAE の概要

• エントリーDOI: 10.2210/pdb8hae/pdb
• EMDBエントリー: 34586
• 分子名称: E3 ubiquitin-protein ligase HACE1 (1 entity in total)
• 機能のキーワード: e3 ubiquitin ligase, tumor suppressor, post-translational modifier, protein degradation, antitumor protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 204899.34

構造登録者

Singh, S.,Machida, S.,Tulsian, N.K.,Choong, Y.K.,Ng, J.,Shanker, S.,Yaochen, L.D.,Shi, J.,Sivaraman, J.,Machida, S. (登録日: 2022-10-26, 公開日: 2023-06-28, 最終更新日: 2023-10-04)

主引用文献

Singh, S.,Machida, S.,Tulsian, N.K.,Choong, Y.K.,Ng, J.,Shankar, S.,Liu, Y.,Chandiramani, K.V.,Shi, J.,Sivaraman, J.
Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.
Adv Sci, 10:e2207672-e2207672, 2023

PubMed Abstract: HACE1 is an ankyrin repeat (AKR) containing HECT-type E3 ubiquitin ligase that interacts with and ubiquitinates multiple substrates. While HACE1 is a well-known tumor suppressor, its structure and mode of ubiquitination are not understood. The authors present the cryo-EM structures of human HACE1 along with in vitro functional studies that provide insights into how the enzymatic activity of HACE1 is regulated. HACE1 comprises of an N-terminal AKR domain, a middle (MID) domain, and a C-terminal HECT domain. Its unique G-shaped architecture interacts as a homodimer, with monomers arranged in an antiparallel manner. In this dimeric arrangement, HACE1 ubiquitination activity is hampered, as the N-terminal helix of one monomer restricts access to the C-terminal domain of the other. The in vitro ubiquitination assays, hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis, mutagenesis, and in silico modeling suggest that the HACE1 MID domain plays a crucial role along with the AKRs in RAC1 substrate recognition.

PubMed: 37537642
DOI: 10.1002/advs.202207672

実験手法

ELECTRON MICROSCOPY (4.55 Å)