Mitochondrial leader sequences: Structural similarities and sequence differences
Mitochondrial leader sequences: Structural similarities and sequence differences
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DOI：
10.1002/(sici)1097-010x(199809/10)282:1/2
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发表时间：
1998-10-01
影响因子：
--
通讯作者：
Weiner, H
中科院分区：
文献类型：
--
作者：
Hammen, PK;Weiner, H
虽然基本上没有氨基酸序列的同源性，但不同前蛋白的线粒体前导序列执行相同的功能，将蛋白质靶向线粒体。已经注意到的前导序列的共同属性是净正电荷和形成两亲性α-螺旋的能力。本研究的目的是确定这两个属性在大鼠肝线粒体乙醛脱氢酶前导子序列中的相对重要性。通过定点突变，系统地将精氨酸残基替换为谷氨酰胺。结果发现，单个精氨酸可以在不损失进口能力的情况下被取代，因此不需要前导序列的总电荷来进口前蛋白。然而，当两个精氨酸同时被取代时，特别是Arg3和Arg10，前蛋白失去了输入的能力。通过修改前导序列以显著增加其螺旋形成潜力，恢复了这种能力。该前导序列直到Arg11才含有带正电的侧链。因此，已经证明在前十个残基中不需要正电荷，只要该序列可以形成相对更稳定的α-螺旋。形成两亲性α-螺旋的能力仍然是决定前导序列能否发挥其重要功能的关键因素。J.Exp.祖尔。282：280-283,1998。(C)1998年Wiley-Liss，Inc.
While having essentially no amino acid sequence homology, the mitochondrial leader sequences of different pre-proteins carry out the same function of targeting the protein to mitochondria. Among the common attributes that have been noted for leader sequences are a net positive charge and the ability to form amphiphilic alpha-helices. The aim of the research described here was to determine the relative importance of these two attributes in the leader sequence of rat liver mitochondrial aldehyde dehydrogenase. Through site-directed mutagenesis, arginine residues were systematically replaced by glutamine. It was found that individual arginines could be replaced without loss of import competence, so the total charge of the leader sequence was not required for the pre-protein to be imported. However, when two arginines were replaced simultaneously, especially Arg3 and Arg10, the pre-protein lost the ability to be imported. This ability was restored by modifying the leader sequence to increase dramatically its helix-forming potential. This leader sequence did not contain a positive-charged side-chain until Arg11. Therefore, it has been shown that positive charge is not required in the first ten residues provided the sequence could form a relatively more stable alpha-helix. The ability to form an amphiphilic alpha-helix remains the essential factor in determining whether or not a leader sequence can carry out its import function. J. Exp. Zool. 282:280-283, 1998. (C) 1998 Wiley-Liss, Inc.