Characterization of the Conformational Fluctuations in the Josephin Domain of Ataxin-3

被引：12

作者：

Sanfelice, Domenico ^{[1
]}

De Simone, Alfonso ^{[2
]}

Cavalli, Andrea ^{[3
,4
]}

Faggiano, Serena ^{[1
]}

Vendruscolo, Michele ^{[4
]}

Pastore, Annalisa ^{[5
]}

机构：

[1] Natl Inst Med Res, MRC, London NW7 1AA, England

[2] Univ London Imperial Coll Sci Technol & Med, Div Mol Biosci, London, England

[3] Inst Res Biomed, CH-6500 Bellinzona, Switzerland

[4] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

[5] Kings Coll London, Dept Basic & Clin Neurosci, London WC2R 2LS, England

来源：

BIOPHYSICAL JOURNAL | 2014年 / 107卷 / 12期

基金：

美国国家卫生研究院;

关键词：

POLYGLUTAMINE DISEASE PROTEIN; NMR CHEMICAL-SHIFTS; DEUBIQUITINATING ENZYME ATAXIN-3; AVERAGED STRUCTURAL RESTRAINTS; MOLECULAR-DYNAMICS SIMULATIONS; RESIDUAL DIPOLAR COUPLINGS; FUNCTIONAL-ANALYSIS; ENERGY LANDSCAPES; UBIQUITIN-BINDING; FORCE-FIELDS;

D O I：

10.1016/j.bpj.2014.10.008

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

As for a variety of other molecular recognition processes, conformational fluctuations play an important role in the cleavage of polyubiquitin chains by the Josephin domain of ataxin-3. The interaction between Josephin and ubiquitin appears to be mediated by the motions of alpha-helical hairpin that is unusual among deubiquitinating enzymes. Here, we characterized the conformational fluctuations of the helical hairpin by incorporating NMR measurements as replica-averaged restraints in molecular dynamics simulations, and by validating the results by small-angle x-ray scattering measurements. This approach allowed us to define the extent of the helical hairpin motions and suggest a role of such motions in the recognition of ubiquitin.

引用

页码：2923 / 2931

页数：9

共 50 条

[41] Trehalose prevents the formation of aggregates of mutant ataxin-3 and reduces soluble ataxin-3 protein levels in an SCA3 cell model
Wang, Zijian
Wang, Min
Huang, Yuhang
Ma, Zhiwei
Gao, Wenjing
Zhang, Tian
Deng, Jiexin
Cheng, Xiaoxia
Liu, Yingxun
Wang, Bo
Qi, Ying
Yang, Min
He, Fengqin
NEUROSCIENCE, 2024, 555 : 76 - 82
[42] Conformational fluctuations of the AXH monomer of Ataxin-1
Grasso, Gianvito
Deriu, Marco A.
Tuszynski, Jack A.
Gallo, Diego
Morbiducci, Umberto
Danani, Andrea
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2016, 84 (01) : 52 - 59
[43] NEDD8:: A new ataxin-3 interactor
Ferro, Anabela
Carvalho, Ana Luisa
Teixeira-Castro, Andrela
Almeida, Carla
Tome, Ricardo J.
Cortes, Luisa
Rodrigues, Ana-Joao
Logarinho, Elsa
Sequeiros, Jorge
Macedo-Ribeiro, Sandra
Maciel, Patricia
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2007, 1773 (11): : 1619 - 1627
[44] RNA toxicity is a component of ataxin-3 degeneration in Drosophila
Li, Ling-Bo
Yu, Zhenming
Teng, Xiuyin
Bonini, Nancy M.
NATURE, 2008, 453 (7198) : 1107 - U9
[45] Proteotoxic stress increases nuclear localization of ataxin-3
Reina, Christopher P.
Zhong, Xiaoyan
Pittman, Randall N.
HUMAN MOLECULAR GENETICS, 2010, 19 (02) : 235 - 249
[46] EVOLUTIONARY HISTORY AND GENE EXPRESSION OF ATAXIN-3 PARALOGS
Felicio, Daniela
Martins, Maria Ines
Pinto, Andreia
Costa, Ines P. D.
Amorim, Antonio
Lopes, Alexandra M.
Seixas, Susana
Martins, Sandra
MEDICINE, 2025, 104 (04)
[47] Ataxin-3 is transported into the nucleus and associates with the nuclear matrix
Tait, D
Riccio, M
Sittler, A
Scherzinger, E
Santi, S
Ognibene, A
Maraldi, NM
Lehrach, H
Wanker, EE
HUMAN MOLECULAR GENETICS, 1998, 7 (06) : 991 - 997
[48] RNA toxicity is a component of ataxin-3 degeneration in Drosophila
Ling-Bo Li
Zhenming Yu
Xiuyin Teng
Nancy M. Bonini
Nature, 2008, 453 : 1107 - 1111
[49] SUMO-1共价修饰ataxin-3
汤建光
沈璐
唐北沙
张玉虎
江泓
廖书胜
张海南
王春喻
夏昆
潘乾
生物化学与生物物理进展, 2006, (11) : 1037 - 1043
[50] Covalent modification of ataxin-3 by SUMO-1
Tang Jian-Guang
Shen Lu
Tang Bei-Sha
Zhang Yu-Hu
Jiang Hong
Liao Shu-Sheng
Zhang Hai-Nan
Wang Chun-Yu
Xia Kun
Pan Qian
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS, 2006, 33 (11) : 1037 - 1043

← 1 2 3 4 5 →