8IC9

Lys48-linked K48C-diubiquitin

8IC9 の概要

• エントリーDOI: 10.2210/pdb8ic9/pdb
• 分子名称: Polyubiquitin-B, Ubiquitin (3 entities in total)
• 機能のキーワード: ubiquitin, isopeptide bond, signaling protein
• 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: 34255.25

構造登録者

Hiranyakorn, M.,Yagi-Utsumi, M.,Yanaka, S.,Ohtsuka, N.,Momiyama, N.,Satoh, T.,Kato, K. (登録日: 2023-02-11, 公開日: 2023-04-26, 最終更新日: 2024-05-29)

主引用文献

Hiranyakorn, M.,Yagi-Utsumi, M.,Yanaka, S.,Ohtsuka, N.,Momiyama, N.,Satoh, T.,Kato, K.
Mutational and Environmental Effects on the Dynamic Conformational Distributions of Lys48-Linked Ubiquitin Chains.
Int J Mol Sci, 24:-, 2023

PubMed Abstract: In multidomain proteins, individual domains connected by flexible linkers are dynamically rearranged upon ligand binding and sensing changes in environmental factors, such as pH and temperature. Here, we characterize dynamic domain rearrangements of Lys48-linked ubiquitin (Ub) chains as models of multidomain proteins in which molecular surfaces mediating intermolecular interactions are involved in intramolecular domain-domain interactions. Using NMR and other biophysical techniques, we characterized dynamic conformational interconversions of diUb between open and closed states regarding solvent exposure of the hydrophobic surfaces of each Ub unit, which serve as binding sites for various Ub-interacting proteins. We found that the hydrophobic Ub-Ub interaction in diUb was reinforced by cysteine substitution of Lys48 of the distal Ub unit because of interaction between the cysteinyl thiol group and the C-terminal segment of the proximal Ub unit. In contrast, the replacement of the isopeptide linker with an artificial ethylenamine linker minimally affected the conformational distributions. Furthermore, we demonstrated that the mutational modification allosterically impacted the exposure of the most distal Ub unit in triUb. Thus, the conformational interconversion of Ub chains offers a unique design framework in Ub-based protein engineering not only for developing biosensing probes but also for allowing new opportunities for the allosteric regulation of multidomain proteins.

PubMed: 37047047
DOI: 10.3390/ijms24076075

実験手法

X-RAY DIFFRACTION (1.25 Å)