Artículo
Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
Fecha de publicación:
01/2011
Editorial:
Oxford University Press
Revista:
Protein Engineering Design & Selection
ISSN:
1741-0126
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Kinetic partitioning between competing routes is present in many biological processes. Here, we propose a methodology to characterize kinetic partitioning through site-directed mutagenesis and apply it to parallel routes for unfolding of the TI I27 protein and for recognition of its target DNA by the human papillomavirus E2 protein. The balance between the two competing reaction routes can be quantified by the partitioning constant K(p). K(p) is easily modulated by point mutations, opening the way for the rational design of kinetic partitioning. Conserved wild-type residues strongly favor one of the two competing reactions, suggesting that in these systems there is an evolutionary pressure to shift partitioning towards a certain route. The mutations with the largest effects on partitioning cluster together in space, defining the protein regions most relevant for the modulation of partitioning. Such regions are neither fully coincident with nor strictly segregated from the regions that are important from each competing reaction. We dissected the mutational effects on partitioning into the contributions from each competing route using a new parameter called pi-value. The results suggest how the design of kinetic partitioning may be approached in each case.
Palabras clave:
Kinetic Partitioning
,
Point Mutation
,
Protein Design
,
Protein-Dna Binding
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Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos(OCA CIUDAD UNIVERSITARIA)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA
Citación
Sánchez Miguel, Ignacio Enrique; Ferreiro, Diego; de Prat Gay, Gonzalo; Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding; Oxford University Press; Protein Engineering Design & Selection; 24; 1-2; 1-2011; 179-184
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