Mia40 is optimized for function in mitochondrial oxidative protein folding and import.
Mia40 is optimized for function in mitochondrial oxidative protein folding and import.
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Mia40 针对线粒体氧化蛋白折叠和导入功能进行了优化
DOI：
10.1021/cb500408n
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发表时间：
2014
影响因子：
4
通讯作者：
F. X. Schmid
中科院分区：
文献类型：
--
作者：
J. R. Koch ;F. X. Schmid
Mia40催化线粒体中的氧化蛋白质折叠。它含有独特的催化CPC二硫醇，两侧是疏水沟，与其他氧化还原酶不同，它与底物形成长寿命的混合二硫化物。我们发现，这种独特的属性既不源于线粒体底物的特定属性，也不源于Mia40的CPC基序。Mia40的催化半胱氨酸显示出异常低的化学反应性，如以常规的pK值和还原电位表示的。混合二硫化物中间体的稳定性与Mia40和底物之间的疏水相互作用在能量上耦合。基于这些特性，我们提出了Mia40的一种机制，其中采用疏水结合位点来选择底物硫醇以形成初始混合二硫化物。它的长寿命用于保留线粒体中部分折叠的蛋白质，并指导折叠形成天然二硫键。
Mia40 catalyzes oxidative protein folding in mitochondria. It contains a unique catalytic CPC dithiol flanked by a hydrophobic groove, and unlike other oxidoreductases, it forms long-lived mixed disulfides with substrates. We show that this distinctive property originates neither from particular properties of mitochondrial substrates nor from the CPC motif of Mia40. The catalytic cysteines of Mia40 display unusually low chemical reactivity, as expressed in conventional pKvalues and reduction potentials. The stability of the mixed disulfide intermediate is coupled energetically with hydrophobic interactions between Mia40 and the substrate. Based on these properties, we suggest a mechanism for Mia40, where the hydrophobic binding site is employed to select a substrate thiol for forming the initial mixed disulfide. Its long lifetime is used to retain partially folded proteins in the mitochondria and to direct folding toward forming the native disulfide bonds.