After mild reduction of serum albumin, seven among the 34 cysteines forming the disulfide network displayed a surprising hyper-reactivity. Compared to the thiol group of glutathione, the average reactivity of these cysteines towards disulfides and thiol reagents was more than 100 times higher. Using mass spectrometry and kinetic data, we identified all these unusual residues, with Cys75, Cys123 and Cys264 showing the highest reactivity. This effect was mainly due to a low pKa of the sulfhydryl groups and may explain the very fast formation of early disulfides in the nascent protein suggesting the existence of a hierarchical propensity to form such covalent links in selected regions during oxidative folding. An identical pattern of hyper-reactive cysteines was found in albumins from six different mammals. This hyper-reactivity is much higher than the one found in other proteins containing multiple cysteines only devoted to structural disulfide bonds. It is possible that such hyper-reactive cysteines could also be present in other proteins, although their existence has been completely ignored so far.

Bocedi, A., Fabrini, R., Pedersen, J.z., Federici, G., Iavarone, F., Martelli, C., et al. (2016). The extreme hyper-reactivity of selected cysteines drives hierarchical disulfide bond formation in serum albumin. THE FEBS JOURNAL, 283(22), 4113-4127 [10.1111/febs.13909].

The extreme hyper-reactivity of selected cysteines drives hierarchical disulfide bond formation in serum albumin

Bocedi, A;FABRINI, RAFFAELE;PEDERSEN, JENS ZACHO;FEDERICI, GIORGIO;CASTAGNOLA, MASSIMO;RICCI, GIORGIO
2016

Abstract

After mild reduction of serum albumin, seven among the 34 cysteines forming the disulfide network displayed a surprising hyper-reactivity. Compared to the thiol group of glutathione, the average reactivity of these cysteines towards disulfides and thiol reagents was more than 100 times higher. Using mass spectrometry and kinetic data, we identified all these unusual residues, with Cys75, Cys123 and Cys264 showing the highest reactivity. This effect was mainly due to a low pKa of the sulfhydryl groups and may explain the very fast formation of early disulfides in the nascent protein suggesting the existence of a hierarchical propensity to form such covalent links in selected regions during oxidative folding. An identical pattern of hyper-reactive cysteines was found in albumins from six different mammals. This hyper-reactivity is much higher than the one found in other proteins containing multiple cysteines only devoted to structural disulfide bonds. It is possible that such hyper-reactive cysteines could also be present in other proteins, although their existence has been completely ignored so far.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
Con Impact Factor ISI
Serum albumin; disulfide; hyper-reactivity of cysteines; oxidative folding; protein structure
Bocedi, A., Fabrini, R., Pedersen, J.z., Federici, G., Iavarone, F., Martelli, C., et al. (2016). The extreme hyper-reactivity of selected cysteines drives hierarchical disulfide bond formation in serum albumin. THE FEBS JOURNAL, 283(22), 4113-4127 [10.1111/febs.13909].
Bocedi, A; Fabrini, R; Pedersen, Jz; Federici, G; Iavarone, F; Martelli, C; Castagnola, M; Ricci, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/170162
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