6DO4

KLHDC2 ubiquitin ligase in complex with SelS C-end degron

6DO4 の概要

• エントリーDOI: 10.2210/pdb6do4/pdb
• 分子名称: Kelch domain-containing protein 2, SELS C-END DEGRON (3 entities in total)
• 機能のキーワード: kelch repeat, beta-propeller, degron, complex, substrate receptor, e3, ubiquitin ligase, 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: 83623.16

構造登録者

Rusnac, D.V.,Lin, H.C.,Yen, H.C.S.,Zheng, N. (登録日: 2018-06-08, 公開日: 2018-12-19, 最終更新日: 2023-10-11)

主引用文献

Rusnac, D.V.,Lin, H.C.,Canzani, D.,Tien, K.X.,Hinds, T.R.,Tsue, A.F.,Bush, M.F.,Yen, H.S.,Zheng, N.
Recognition of the Diglycine C-End Degron by CRL2KLHDC2Ubiquitin Ligase.
Mol. Cell, 72:813-822.e4, 2018

PubMed Abstract: Aberrant proteins can be deleterious to cells and are cleared by the ubiquitin-proteasome system. A group of C-end degrons that are recognized by specific cullin-RING ubiquitin E3 ligases (CRLs) has recently been identified in some of these abnormal polypeptides. Here, we report three crystal structures of a CRL2 substrate receptor, KLHDC2, in complex with the diglycine-ending C-end degrons of two early-terminated selenoproteins and the N-terminal proteolytic fragment of USP1. The E3 recognizes the degron peptides in a similarly coiled conformation and cradles their C-terminal diglycine with a deep surface pocket. By hydrogen bonding with multiple backbone carbonyls of the peptides, KLHDC2 further locks in the otherwise degenerate degrons with a compact interface and unexpected high affinities. Our results reveal the structural mechanism by which KLHDC2 recognizes the simplest C-end degron and suggest a functional necessity of the E3 to tightly maintain the low abundance of its select substrates.

PubMed: 30526872
DOI: 10.1016/j.molcel.2018.10.021

実験手法

X-RAY DIFFRACTION (2.2 Å)