Potassium and the K+/H+ Exchanger Kha1p Promote Binding of Copper to ApoFet3p Multi-copper Ferroxidase

钾和K+/H+交换蛋白Kha1p促进铜与ApoFet3p多铜铁氧化酶的结合

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作者:Xiaobin Wu ,Heejeong Kim ,Javier Seravalli ,Joseph J Barycki ,P John Hart ,David W Gohara ,Enrico Di Cera ,Won Hee Jung ,Daniel J Kosman ,Jaekwon Lee

Abstract

Acquisition and distribution of metal ions support a number of biological processes. Here we show that respiratory growth of and iron acquisition by the yeast Saccharomyces cerevisiae relies on potassium (K(+)) compartmentalization to the trans-Golgi network via Kha1p, a K(+)/H(+) exchanger. K(+) in the trans-Golgi network facilitates binding of copper to the Fet3p multi-copper ferroxidase. The effect of K(+) is not dependent on stable binding with Fet3p or alteration of the characteristics of the secretory pathway. The data suggest that K(+) acts as a chemical factor in Fet3p maturation, a role similar to that of cations in folding of nucleic acids. Up-regulation of KHA1 gene in response to iron limitation via iron-specific transcription factors indicates that K(+) compartmentalization is linked to cellular iron homeostasis. Our study reveals a novel functional role of K(+) in the binding of copper to apoFet3p and identifies a K(+)/H(+) exchanger at the secretory pathway as a new molecular factor associated with iron uptake in yeast. Keywords: copper; ferroxidase; iron; iron response element (IRE); potassium transport; protein secretion.

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