Artículo
Structural analysis of a natural apolipoprotein A-I variant (L60R) associated with amyloidosis
Gaddi, Gisela Marina
; Gisonno, Romina Antonela
; Rosu, Silvana Antonia
; Curto, Lucrecia María
; Prieto, Eduardo Daniel
; Schinella, Guillermo Raúl; Finarelli, Gabriela Sandra; Cortez, María Fernanda
; Bauzá, Letizia
; Elías, Esteban Enrique
; Ramella, Nahuel
; Tricerri, Maria Alejandra
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Fecha de publicación:
30/05/2020
Editorial:
Elsevier Science Inc.
Revista:
Archives of Biochemistry and Biophysics
ISSN:
0003-9861
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The reason that determines the pathological deposition of human apolipoprotein A-I variants inducing organ failure has been under research since the early description of natural mutations in patients. To shed light into the events associated with protein aggregation, we studied the structural perturbations that may occur in the natural variant that shows a substitution of a Leucine by an Arginine in position 60 (L60R). Circular dichroism, intrinsic fluorescence measurements, and proteolysis analysis indicated that L60R was more unstable, more sensitive to cleavage and the N-terminus was more disorganized than the protein with the native sequence (Wt). A higher tendency to aggregate was also detected when L60R was incubated at physiological pH. In addition, the small structural rearrangement observed for the freshly folded variant led to the release of tumor necrosis factor-α and interleukin-1β from a model of macrophages. However, the mutant preserved both its dimeric conformation and its lipid-binding capacity. Our results strongly suggest that the chronic disease may be a consequence of the native conformation loss which elicits the release of protein conformations that could be either cytotoxic or precursors of amyloid conformations.
Palabras clave:
AMYLOIDOSIS
,
APOLIPOPOPROTEIN A-I
,
INFLAMMATION
,
PROTEIN MISFOLDING
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Identificadores
Colecciones
Articulos(INIBIOLP)
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Citación
Gaddi, Gisela Marina; Gisonno, Romina Antonela; Rosu, Silvana Antonia; Curto, Lucrecia María; Prieto, Eduardo Daniel; et al.; Structural analysis of a natural apolipoprotein A-I variant (L60R) associated with amyloidosis; Elsevier Science Inc.; Archives of Biochemistry and Biophysics; 685; 30-5-2020; 1-11
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