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

详细信息    查看全文

• 作者：Alessio Bocedi ; Raffaele Fabrini ; Jens Z. Pedersen ; Giorgio Federici ; Federica Iavarone ; Claudia Martelli ; Massimo Castagnola ; Giorgio Ricci
• 刊名：FEBS Journal
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：283
• 期：22
• 页码：4113-4127
• 全文大小：1.4MB
• ISSN：1742-4658

文摘

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 pK_a 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.