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
收藏
页码：2923 / 2931
页数：9
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