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

Federica Iavarone, Claudia Martelli, Massimo Castagnola, Alessio Bocedi, Raffaele Fabrini, Jens Z. Pedersen, Giorgio Federici, Giorgio Ricci

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

11 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)4113-4127
Numero di pagine15
RivistaTHE FEBS JOURNAL
Volume2016
Stato di pubblicazionePubblicato - 2016

Keywords

  • Albumin

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