5NLF

Crystal structure of Zn2.7-E16V human ubiquitin (hUb) mutant adduct, from a solution 100 mM zinc acetate/1.3 mM E16V hUb

5NLF の概要

• エントリーDOI: 10.2210/pdb5nlf/pdb
• 関連するPDBエントリー: 3EHV 4K7W 4KTS 4KTU
• 分子名称: Polyubiquitin-C, ZINC ION, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: e16v mutant, ligase, ubiquitination, proteasome degradation, immune system
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Ubiquitin: Cytoplasm : P0CG48
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 26589.85

構造登録者

Fermani, S.,Falini, G. (登録日: 2017-04-04, 公開日: 2017-05-03, 最終更新日: 2024-01-17)

主引用文献

Fermani, S.,Calvaresi, M.,Mangini, V.,Falini, G.,Bottoni, A.,Natile, G.,Arnesano, F.
Aggregation Pathways of Native-Like Ubiquitin Promoted by Single-Point Mutation, Metal Ion Concentration, and Dielectric Constant of the Medium.
Chemistry, 24:4140-4148, 2018

PubMed Abstract: Ubiquitin-positive protein aggregates are biomarkers of neurodegeneration, but the molecular mechanism responsible for their formation and accumulation is still unclear. Possible aggregation pathways of human ubiquitin (hUb) promoted by both intrinsic and extrinsic factors, are here investigated. By a computational analysis, two different hUb dimers are indicated as possible precursors of amyloid-like structures, but their formation is disfavored by an electrostatic repulsion involving Glu16 and other carboxylate residues present at the dimer interface. Experimental data on the E16V mutant of hUb shows that this single-point mutation, although not affecting the overall protein conformation, promotes protein aggregation. It is sufficient to shift the same mutation by only two residues (E18V) to regain the behavior of wild-type hUb. The neutralization of Glu16 negative charge by a metal ion and a decrease of the dielectric constant of the medium by addition of trifluoroethanol (TFE), also promote hUb aggregation. The outcomes of this research have important implications for the prediction of physiological parameters that favor aggregate formation.

PubMed: 29266436
DOI: 10.1002/chem.201705543

実験手法

X-RAY DIFFRACTION (1.5 Å)