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Published Online February 9, 2006
Science DOI: 10.1126/science.1123809

Research Articles

Submitted on December 13, 2005
Accepted on January 30, 2006

Structure of the Hydrophilic Domain of Respiratory Complex I from Thermus thermophilus

Leonid A. Sazanov 1* and Philip Hinchliffe 1

1 Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, U.K.

* To whom correspondence should be addressed.
Leonid A. Sazanov , E-mail: sazanov{at}mrc-dunn.cam.ac.uk

Respiratory complex I plays a central role in cellular energy production in bacteria and mitochondria. Its dysfunction is implicated in many human neurodegenerative diseases, as well as in aging. The crystal structure of the hydrophilic domain (peripheral arm) of complex I from Thermus thermophilus has been solved at 3.3 angstrom resolution. This subcomplex consists of eight subunits and contains all the redox centers of the enzyme, including nine iron-sulfur clusters. The primary electron acceptor, flavin-mononucleotide, is within electron transfer distance to cluster N3, leading to the main redox pathway, and to the distal cluster N1a, a possible anti-oxidant. The structure reveals new aspects of the mechanism and evolution of the enzyme. The terminal cluster N2 is coordinated, uniquely, by two consecutive cysteines. The novel subunit Nqo15 has a similar fold to the mitochondrial iron chaperone frataxin and it may be involved in iron-sulfur cluster regeneration in the complex.


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