Artículo
The role of the N-terminal tail for the oligomerization, folding and stability of human frataxin
Faraj, Santiago Enrique
; Venturutti, Leandro
; Roman, Ernesto Andres
; Marino, Cristina Ester
; Mignone, Astor; Tosatto, Silvio C.E.; Delfino, Jose Maria
; Santos, Javier
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Fecha de publicación:
07/2013
Editorial:
Elsevier
Revista:
FEBS Open Bio
ISSN:
2211-5463
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The N-terminal stretch of human frataxin (hFXN) intermediate (residues 42?80) is not conserved throughout evolution and, under defined experimental conditions, behaves as a random-coil. Overexpression of hFXN56?210 in E. coli yields a multimer, whereas the mature form of hFXN (hFXN81?210) is monomeric. Thus, cumulative experimental evidence points to the N-terminal moiety as an essential element for the assembly of a high molecular weight oligomer. The secondary structure propensity of peptide 56?81, the moiety putatively responsible for promoting protein-protein interactions, was also studied. Depending on the environment (TFE or SDS), this peptide adopts α-helical or β-strand structure. In this context, we explored the conformation and stability of hFXN56?210. The biophysical characterization by fluorescence, CD and SEC‑FPLC shows that subunits are well folded, sharing similar stability to hFXN90?210. However, controlled proteolysis indicates that the N-terminal stretch is labile in the context of the multimer, whereas the FXN domain (residues 81?210) remains strongly resistant. In addition, guanidine hydrochloride at low concentration disrupts intermolecular interactions, shifting the ensemble toward the monomeric form. The conformational plasticity of the N-terminal tail might impart on hFXN the ability to act as a recognition signal as well as an oligomerization trigger. Understanding the fine-tuning of these activities and their resulting balance will bear direct relevance for ultimately comprehending hFXN function.
Palabras clave:
FRATAXIN
,
HELICAL PROPENSITY
,
PROTEIN STABILITY
,
OLIGOMERIZATION
,
FOLDING
Archivos asociados
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Identificadores
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
Faraj, Santiago Enrique; Venturutti, Leandro; Roman, Ernesto Andres; Marino, Cristina Ester; Mignone, Astor; et al.; The role of the N-terminal tail for the oligomerization, folding and stability of human frataxin; Elsevier; FEBS Open Bio; 3; 3; 7-2013; 310-320
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