6CCU

Complex between a GID4 fragment and a short peptide

6CCU の概要

• エントリーDOI: 10.2210/pdb6ccu/pdb
• 分子名称: Glucose-induced degradation protein 4 homolog, Short peptide, UNKNOWN ATOM OR ION, ... (4 entities in total)
• 機能のキーワード: structural genomics, structural genomics consortium, sgc, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22248.78

構造登録者

Dong, C.,Tempel, W.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (登録日: 2018-02-07, 公開日: 2018-03-07, 最終更新日: 2023-10-04)

主引用文献

Dong, C.,Zhang, H.,Li, L.,Tempel, W.,Loppnau, P.,Min, J.
Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway.
Nat. Chem. Biol., 14:466-473, 2018

PubMed Abstract: The N-end rule pathway senses the N-terminal destabilizing residues of degradation substrates for the ubiquitin-proteasome system, whose integrity shields against various human syndromes including cancer and cardiovascular diseases. GID4, a subunit of the ubiquitin ligase GID complex, has been recently identified as the N-recognin of the new branch of the N-end rule pathway responsible for recognizing substrates bearing N-terminal proline residues (Pro/N-degrons). However, the molecular mechanism of GID4-mediated Pro/N-degron recognition remains largely unexplored. Here, we report the first crystal structures of human GID4 alone and in complex with various Pro/N-degrons. Our complex crystal structures, together with biophysical analyses, delineate the GID4-mediated Pro/N-degron recognition mechanism and substrate selection criteria for the Pro/N-end rule pathway. These mechanistic data on the Pro/N-recognin activity of GID4 will serve as a foundation to facilitate the identification of authentic physiological substrates as well as the development of inhibitors of therapeutic values for the Pro/N-end rule pathway.

PubMed: 29632410
DOI: 10.1038/s41589-018-0036-1

実験手法

X-RAY DIFFRACTION (1.75 Å)