Unveiling the folding mechanism of the Bromodomains

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dc.contributor.author Pasquo, A.
dc.date.accessioned 2017-09-08T12:46:54Z
dc.date.available 2017-09-08T12:46:54Z
dc.date.issued 2017
dc.identifier.issn 2405-5808
dc.identifier.uri http://hdl.handle.net/10840/8871
dc.description.abstract Bromodomains (BRDs) are small protein domains often present in large multidomain proteins involved in transcriptional regulation in eukaryotic cells. They currently represent valuable targets for the development of inhibitors of aberrant transcriptional processes in a variety of human diseases. Here we report urea-induced equilibrium unfolding experiments monitored by circular dichroism (CD) and fluorescence on two structurally similar BRDs: BRD2(2) and BRD4(1), showing that BRD4(1) is more stable than BRD2(2). Moreover, we report a description of their kinetic folding mechanism, as obtained by careful analysis of stopped-flow and temperature-jump data. The presence of a high energy intermediate for both proteins, suggested by the non-linear dependence of the folding rate on denaturant concentration in the millisec time regime, has been experimentally observed by temperature-jump experiments. Quantitative global analysis of all the rate constants obtained over a wide range of urea concentrations, allowed us to propose a common, three-state, folding mechanism for these two BRDs. Interestingly, the intermediate of BRD4(1) appears to be more stable and structurally native-like than that populated by BRD2(2). Our results underscore the role played by structural topology and sequence in determining and tuning the folding mechanism. © 2017 The Authors it_IT
dc.language.iso en it_IT
dc.publisher Elsevier B.V. it_IT
dc.relation.ispartof Biochemistry and Biophysics Reports it_IT
dc.title Unveiling the folding mechanism of the Bromodomains it_IT
dc.type Articolo su rivista it_IT
dc.description.riferimenti Scopus ID: 2-s2.0-85023615140
dc.description.sede-enea Centro Ricerche Casaccia it_IT
dc.relation.pagenumber 99 - 104 it_IT
dc.relation.volumenumber 11 it_IT
dc.subject.keywords Bromodomain it_IT
dc.subject.keywords Folding intermediate it_IT
dc.subject.keywords Protein folding it_IT
dc.subject.tipologia-enea Biologia delle Radiazioni e Salute dell'uomo it_IT
dc.description.info Authors: Petrosino M., Bonetti D., Pasquo A., Lori L., Chiaraluce R., Consalvi V., Travaglini-Allocatelli C. it_IT
dc.identifier.doi 10.1016/j.bbrep.2017.06.009
dc.identifier.url https://www.scopus.com/inward/record.uri?eid=2-s2.0-85023615140&doi=10.1016%2fj.bbrep.2017.06.009&partnerID=40&md5=492d2a0909d1a1543c8bc9e0293e4ed7

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