5TDC

Crystal structure of the human UBR-box domain from UBR1 in complex with monomethylated arginine peptide.

5TDC の概要

• エントリーDOI: 10.2210/pdb5tdc/pdb
• 関連するPDBエントリー: 5TDA 5TDB 5TDD
• 分子名称: E3 ubiquitin-protein ligase UBR1, NMM-ILE-PHE-SER peptide, ZINC ION, ... (5 entities in total)
• 機能のキーワード: ubr-box, n-end rule, n-degron, monomethylated arginine, 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: 18298.63

構造登録者

Kozlov, G.,Munoz-Escobar, J.,Matta-Camacho, E.,Gehring, K. (登録日: 2016-09-19, 公開日: 2017-03-22, 最終更新日: 2023-10-04)

主引用文献

Munoz-Escobar, J.,Matta-Camacho, E.,Cho, C.,Kozlov, G.,Gehring, K.
Bound Waters Mediate Binding of Diverse Substrates to a Ubiquitin Ligase.
Structure, 25:719-729.e3, 2017

PubMed Abstract: The N-end rule pathway controls the half-life of proteins based on their N-terminal residue. Positively charged type 1 N-degrons are recognized by a negatively charged pocket on the Zn finger named the UBR box. Here, we show that the UBR box is rigid, but bound water molecules in the pocket provide the structural plasticity required to bind different positively charged amino acids. Ultra-high-resolution crystal structures of arginine, histidine, and methylated arginine reveal that water molecules mediate the binding of N-degron peptides. Using a high-throughput binding assay and isothermal titration calorimetry, we demonstrate that the UBR box is able to bind methylated arginine and lysine peptides with high affinity and measure the preference for hydrophobic residues in the second position in the N-degron peptide. Finally, we show that the V122L mutation present in Johanson-Blizzard syndrome patients changes the specificity for the second position due to occlusion of the secondary pocket.

PubMed: 28392261
DOI: 10.1016/j.str.2017.03.004

実験手法

X-RAY DIFFRACTION (1.607 Å)