2LQ7

E2 binding surface on Uba3 beta-grasp domain undergoes a conformational transition

2LQ7 の概要

• エントリーDOI: 10.2210/pdb2lq7/pdb
• NMR情報: BMRB: 18297
• 分子名称: NEDD8-activating enzyme E1 catalytic subunit (1 entity in total)
• 機能のキーワード: e1 enzyme, beta grasp domain, ligase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10658.07

構造登録者

Elgin, E.S.,Peterson, F.C.,Volkman, B.F. (登録日: 2012-02-27, 公開日: 2012-07-25, 最終更新日: 2024-05-15)

主引用文献

Elgin, E.S.,Sokmen, N.,Peterson, F.C.,Volkman, B.F.,Dag, C.,Haas, A.L.
E2-binding surface on Uba3 beta-grasp domain undergoes a conformational transition.
Proteins, 80:2482-2487, 2012

PubMed Abstract: The covalent attachment of ubiquitin (Ub) and ubiquitin-like (Ubl) proteins to various eukaryotic targets plays critical roles in regulating numerous cellular processes. E1-activating enzymes are critical, because they catalyze activation of their cognate Ub/Ubl protein and are responsible for its transfer to the correct E2-conjugating enzyme(s). The activating enzyme for neural-precursor-cell-expressed developmentally downregulated 8 (NEDD8) is a heterodimer composed of APPBP1 and Uba3 subunits. The carboxyl terminal ubiquitin-like β-grasp domain of human Uba3 (Uba3-βGD) has been suggested as a key E2-binding site defining E2 specificity. In crystal structures of free E1 and the NEDD8-E1 complex, the E2-binding surface on the domain was missing from the electron density. However, when complexed with various E2s, this missing segment adopts a kinked α-helix. Here, we demonstrate that Uba3-βGD is an independently folded domain in solution and that residues involved in E2 binding are absent from the NMR spectrum, indicating that the E2-binding surface on Uba3-βGD interconverts between multiple conformations, analogous to a similar conformational transition observed in the E2-binding surface of SUMO E1. These results suggest that access to multiple conformational substates is an important feature of the E1-E2 interaction.

PubMed: 22821745
DOI: 10.1002/prot.24148

実験手法

SOLUTION NMR