The T9176G mutation of human mtDNA gives a fully assembled but inactive ATP synthase when modeled in Escherichia coli
The T9176G mutation of human mtDNA gives a fully assembled but inactive ATP synthase when modeled in Escherichia coli
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DOI：
10.1016/s0014-5793(00)02244-4
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发表时间：
2000-12-15
期刊：
影响因子：
3.5
通讯作者：
Capaldi, RA
中科院分区：
文献类型：
--
作者：
Carrozzo, R;Murray, J;Capaldi, RA
在患有Leigh综合征的两个兄弟姐妹中描述了人F1F0 ATP酶6 T9176G的新突变，其将Leu 217变为Arg [Carrozzo et al.（2000）Neurology，in press]。通过将Leu 259（等效残基）改变为Arg，在大肠杆菌中模拟了这种突变，并将改变的ECF 1F0的性质与先前在大肠杆菌中模拟的ATPase6突变体的性质进行了比较。大肠杆菌酶。L259R的变化产生了完全组装的ECF1F0，其没有显著的ATP水解、ATP合成或质子泵功能。这与先前描述的人类ATPase6突变非常不同。在亚基a中259位的Arg的存在不使膜对质子具有渗透性。我们的结论是，突变通过阻断酶的旋转马达作用来抑制功能。(C)2000年欧洲生物化学学会联合会。由Elsevier Science B.V.出版，版权所有。
A new mutation in human F1F0 ATPase6 T9176G, which changes Leu 217 to an Arg, has been described in two siblings with Leigh syndrome [Carrozzo et al. (2000) Neurology, in press]. This mutation was modeled in Escherichia coli by changing Leu 259 (the equivalent residue) to Arg and the properties of the altered ECF1F0 were compared to those of previously characterized ATPase6 mutants also modeled in the E. coli enzyme. The L259R change produced a fully assembled ECF1F0 which had no significant ATP hydrolysis, ATP synthesis or proton pumping functions. This is very different from previously described human ATPase6 mutations. The presence of Arg at position 259 in subunit a did not make membranes permeable to protons. We conclude that the mutation inhibits functioning by blocking the rotary motor action of the enzyme. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.