The T9176G mutation of human mtDNA gives a fully assembled but inactive ATP synthase when modeled in Escherichia coli

FEBS Letters

Carrozzo, R.²  Capaldi, R.A.²  Murray, J.²  Santorelli, F.M.¹ 

[1]Unita’ di Medicina Molecolare, Ospedale Pediatrico ‘Bambino Gesu’, Rome 00165, Italy

[2]Institute of Molecular Biology, University of Oregon, Eugene, OR 97403-1229, USA

关键词: F1F0 ATP synthase;    Mitochondrial;    Subunit 6;    T8993G;    Escherichia coli;    ACMA;    9-amino-6-chloro-2-methoxyacridine;    LDAO;    N;    N-dimethyldodecylamine-N-oxide;    DCCD;    dicyclohexylcarbodiimide;    ECF1F0;    Escherichia coli F1F0 ATPase;   

DOI  :  10.1016/S0014-5793(00)02244-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown