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Crystallographic structure of acrchaeal F429H2 dehydrogenase and bacterial NADH; quinone oxidoreductase subcomplexes

Objective

Complex I or NADH: quinone oxidoreductase is the first of 4 membrane-bound enzyme complexes that actively participate in the oxidative phosphorylation process, Electrons transferred from NADH are coupled to proton translocation across a membrane and the resulting electrochemical proton gradient is used to generate ATP. The eucharistic complex I, with about 45 different subunits and over 900 kea, contains one-Man molecule, up to nine Fe/S clusters and at least three-bound quoin! Molecules. Homologs of complex I are present in a vast number of organisms and in prokaryotes their architectures considerably simpler than in eucalypts. Consisting of only 14 subunits, but retaining an equivalent set of cofactors, they represent the minimal requirement for a functional complex I. So far, only a low-resolution 3-Decry electron microscopy structure of complex I am available, showing an L-shaped structure that is conserved between eucalypts and prokaryotes. It is also commonly assumed that complex I have evolved from pre-existing modules for proton translocation and electron transfer. Descriptions of complex I as a \\\\\\\"big black box\\\\\\\" am often found in the literature. Understanding its mechanism is a fundamental challenge in bioenergetics with strong repercussions in medicine. Obtaining structural information on complex I is crucial step towards that goal. However, so far the limited availability of pure and stable material has not allowed for growing suitable crystals for 3-D structure determination by X-ray crystallography. We propose, like it was done in the case of the ribosome, to start out towards getting a complete picture of complex I by looking at isolated subunits or sub complexes and assemble them later with the help of cry electron microscopy images or lower-resolution crystal structures.

Call for proposal

FP6-2002-MOBILITY-5
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Funding Scheme

EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

GEORG-AUGUST-UNIVERSITAET GOETTINGEN
Address
Wilhelmsplatz 1
Goettingen
Germany