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 α-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.

Characterization of the Conformational Fluctuations in the Josephin Domain of Ataxin-3 / Sanfelice, Domenico; De Simone, Alfonso; Cavalli, Andrea; Faggiano, Serena; Vendruscolo, Michele; Pastore, Annalisa. - In: BIOPHYSICAL JOURNAL. - ISSN 0006-3495. - 107:12(2014), pp. 2932-2940. [10.1016/j.bpj.2014.10.008]

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

FAGGIANO, Serena;
2014

Abstract

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 α-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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2817619
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