Cleavage of precursors by the mitochondrial processing peptidase requires a compatible mature protein or an intermediate octapeptide.
Cleavage of precursors by the mitochondrial processing peptidase requires a compatible mature protein or an intermediate octapeptide.
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DOI：
10.1083/jcb.113.1.65
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发表时间：
1991-04
期刊：
影响因子：
--
通讯作者：
Rosenberg LE
中科院分区：
文献类型：
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作者：
Isaya G;Kalousek F;Fenton WA;Rosenberg LE
许多线粒体蛋白的前体在两个连续的步骤中被独立的基质肽酶（MPP和MIP）加工，而其他的则在一个单一的步骤中被MPP单独切割。为了解释这种二分法，我们构建了具有两次切割前体特征的八肽的全部或部分缺失（人鸟氨酸转氨甲酰酶[pOTC]），在一次切割的蛋白质之间交换了前导肽序列。（人甲基丙二酰辅酶A β [pMUT];酵母F1 ATP酶β亚基[pF 1 β]）和两次切割的（pOTC;大鼠苹果酸脱氢酶（pMDH）;脉孢菌泛喹啉-细胞色素c还原酶铁-硫亚基[pFe/S]）前体，并将这些蛋白与纯化的MPP和MIP孵育。当缺失pOTC的八肽时，或者当一次切割的前体（pMUT或pF 1 β）的整个前导肽连接到两次切割的前体（pOTC或pFe/S）的成熟氨基末端时，两种蛋白酶都不产生切割。通过重新插入八肽的少至两个氨基末端残基或一次切割的前体的成熟氨基末端残基来恢复MPP对这些构建体的切割。我们的结论是，成熟的氨基末端的两次裂解的前体是结构上不兼容的MPP裂解，这样的蛋白质已经发展八肽裂解MIP克服这种不兼容性。
Many precursors of mitochondrial proteins are processed in two successive steps by independent matrix peptidases (MPP and MIP), whereas others are cleaved in a single step by MPP alone. To explain this dichotomy, we have constructed deletions of all or part of the octapeptide characteristic of a twice cleaved precursor (human ornithine transcarbamylase [pOTC]), have exchanged leader peptide sequences between once-cleaved (human methylmalonyl-CoA mutase [pMUT]; yeast F1ATPase beta-subunit [pF1 beta]) and twice-cleaved (pOTC; rat malate dehydrogenase (pMDH); Neurospora ubiquinol-cytochrome c reductase iron-sulfur subunit [pFe/S]) precursors, and have incubated these proteins with purified MPP and MIP. When the octapeptide of pOTC was deleted, or when the entire leader peptide of a once-cleaved precursor (pMUT or pF1 beta) was joined to the mature amino terminus of a twice-cleaved precursor (pOTC or pFe/S), no cleavage was produced by either protease. Cleavage of these constructs by MPP was restored by re- inserting as few as two amino-terminal residues of the octapeptide or of the mature amino terminus of a once-cleaved precursor. We conclude that the mature amino terminus of a twice-cleaved precursor is structurally incompatible with cleavage by MPP; such proteins have evolved octapeptides cleaved by MIP to overcome this incompatibility.