3ALB

Cyclic Lys48-linked tetraubiquitin

3ALB の概要

• エントリーDOI: 10.2210/pdb3alb/pdb
• 関連するPDBエントリー: 1AAR 1F9J 1TBE 2O6V
• 分子名称: ubiquitin, SULFATE ION (3 entities in total)
• 機能のキーワード: ubiquitin, tetraubiquitin, isopeptide bond, nucleus, phosphoprotein, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Ubiquitin: Cytoplasm (By similarity): P0CG48
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 34691.58

構造登録者

Satoh, T.,Sakata, E.,Yamamoto, S.,Yamaguchi, Y.,Sumiyoshi, A.,Wakatsuki, S.,Kato, K. (登録日: 2010-07-29, 公開日: 2010-08-25, 最終更新日: 2024-10-30)

主引用文献

Satoh, T.,Sakata, E.,Yamamoto, S.,Yamaguchi, Y.,Sumiyoshi, A.,Wakatsuki, S.,Kato, K.
Crystal structure of cyclic Lys48-linked tetraubiquitin
Biochem.Biophys.Res.Commun., 2010

PubMed Abstract: Lys48-linked polyubiquitin chains serve as a signal for protein degradation by 26S proteasomes through its Ile44 hydrophobic patches interactions. The individual ubiquitin units of each chain are conjugated through an isopeptide bond between Lys48 and the C-terminal Gly76 of the preceding units. The conformation of Lys48-linked tetraubiquitin has been shown to change dynamically depending on solution pH. Here we enzymatically synthesized a wild-type Lys48-linked tetraubiquitin for structural study. In the synthesis, cyclic and non-cyclic species were obtained as major and minor fractions, respectively. This enabled us to solve the crystal structure of tetraubiquitin exclusively with native Lys48-linkages at 1.85A resolution in low pH 4.6. The crystallographic data clearly showed that the C-terminus of the first ubiquitin is conjugated to the Lys48 residue of the fourth ubiquitin. The overall structure is quite similar to the closed form of engineered tetraubiquitin at near-neutral pH 6.7, previously reported, in which the Ile44 hydrophobic patches face each other. The structure of the second and the third ubiquitin units [Ub(2)-Ub(3)] connected through a native isopeptide bond is significantly different from the conformations of the corresponding linkage of the engineered tetraubiquitins, whereas the structures of Ub(1)-Ub(2) and Ub(3)-Ub(4) isopeptide bonds are almost identical to those of the previously reported structures. From these observations, we suggest that the flexible nature of the isopeptide linkage thus observed contributes to the structural arrangements of ubiquitin chains exemplified by the pH-dependent closed-to-open conformational transition of tetraubiquitin.

PubMed: 20728431
DOI: 10.1016/j.bbrc.2010.08.057

実験手法

X-RAY DIFFRACTION (1.85 Å)