MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria
MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria
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DOI：
10.1038/nsmb.1553
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发表时间：
2009-02-01
影响因子：
16.8
通讯作者：
Tokatlidis, Kostas
中科院分区：
文献类型：
--
作者：
Banci, Lucia;Bertini, Ivano;Tokatlidis, Kostas
MIA 40在线粒体膜间隙的氧化蛋白折叠中具有关键作用。我们提出了人MIA 40的溶液结构及其作为氧化折叠催化剂的机制。MIA 40具有66个残基的折叠结构域，其由通过两个结构二硫键和刚性N-末端盖稳定的α-螺旋发夹核心制成，具有特征性CPC基序，其可以将其二硫键提供给底物。CPC活性位点是溶剂可接近的，并且位于疏水裂缝附近。它的第二个半胱氨酸（Cys 55）在体内是必需的，并且对于与底物形成混合二硫键至关重要。疏水裂缝作为底物结合结构域发挥作用，并且该结构域的突变在体内是致命的并且在体外废除结合。MIA 40代表硫氧还蛋白无关的最小氧化还原酶，具有容易的CPC氧化还原活性位点，确保其在线粒体氧化折叠中的催化功能。
MIA40 has a key role in oxidative protein folding in the mitochondrial intermembrane space. We present the solution structure of human MIA40 and its mechanism as a catalyst of oxidative folding. MIA40 has a 66-residue folded domain made of an alpha-helical hairpin core stabilized by two structural disulfides and a rigid N-terminal lid, with a characteristic CPC motif that can donate its disulfide bond to substrates. The CPC active site is solvent-accessible and sits adjacent to a hydrophobic cleft. Its second cysteine (Cys55) is essential in vivo and is crucial for mixed disulfide formation with the substrate. The hydrophobic cleft functions as a substrate binding domain, and mutations of this domain are lethal in vivo and abrogate binding in vitro. MIA40 represents a thioredoxin-unrelated, minimal oxidoreductase, with a facile CPC redox active site that ensures its catalytic function in oxidative folding in mitochondria.