Recent observations indicate that bacterial inclusion bodies formed in absence of the main chaperone DnaK result largely enriched in functional, properly folded recombinant proteins. Unfortunately, the molecular basis of this intriguing fact, with obvious biotechnological interest, remains unsolved. We have explored here two non-excluding physiological mechanisms that could account for this observation, namely selective removal of inactive polypeptides from inclusion bodies or in situ functional activation of the embedded proteins. By combining structural and functional analysis, we have not observed any preferential selection of inactive and misfolded protein species by the dissagregating machinery during inclusion body disintegration. Instead, our data strongly support that folding intermediates aggregated as inclusion bodies could complete their natural folding process once deposited in protein clusters, which conduces to significant functional activation. In addition, in situ folding and protein activation in inclusion bodies is negatively regulated by the chaperone DnaK.

Gonzalez Montalban, N., Natalello, A., García Fruitós, E., Villaverde, A., Doglia, S. (2008). In situ protein folding and activation in bacterial inclusion bodies. BIOTECHNOLOGY AND BIOENGINEERING, 100(4), 797-802 [10.1002/bit.21797].

In situ protein folding and activation in bacterial inclusion bodies

NATALELLO, ANTONINO;DOGLIA, SILVIA MARIA
2008

Abstract

Recent observations indicate that bacterial inclusion bodies formed in absence of the main chaperone DnaK result largely enriched in functional, properly folded recombinant proteins. Unfortunately, the molecular basis of this intriguing fact, with obvious biotechnological interest, remains unsolved. We have explored here two non-excluding physiological mechanisms that could account for this observation, namely selective removal of inactive polypeptides from inclusion bodies or in situ functional activation of the embedded proteins. By combining structural and functional analysis, we have not observed any preferential selection of inactive and misfolded protein species by the dissagregating machinery during inclusion body disintegration. Instead, our data strongly support that folding intermediates aggregated as inclusion bodies could complete their natural folding process once deposited in protein clusters, which conduces to significant functional activation. In addition, in situ folding and protein activation in inclusion bodies is negatively regulated by the chaperone DnaK.
Articolo in rivista - Articolo scientifico
inclusion bodies; protein folding; DnaK; enzymatic activity
English
14-lug-2008
100
4
797
802
none
Gonzalez Montalban, N., Natalello, A., García Fruitós, E., Villaverde, A., Doglia, S. (2008). In situ protein folding and activation in bacterial inclusion bodies. BIOTECHNOLOGY AND BIOENGINEERING, 100(4), 797-802 [10.1002/bit.21797].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/1079
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