TY  - JOUR
A1  - Zickermann, Volker
A1  - Wirth, Christophe
A1  - Nasiri, Hamid Reza
A1  - Siegmund, Karin
A1  - Schwalbe, Harald
A1  - Hunte, Carola
A1  - Brandt, Ulrich
T1  - Mechanistic insight from the crystal structure of mitochondrial complex I
N2  - Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complex membrane protein complexes. The enzyme contributes substantially to oxidative energy-conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders. Here, we report the X-ray structure of mitochondrial complex I at 3.6- 3.9 Å resolution describing in detail the central subunits that execute the bioenergetic function. A continuous axis of basic and acidic residues running centrally through the membrane arm connects the ubiquinone reduction site in the hydrophilic arm to four putative proton-pumping units. The binding position for a substrate analogous inhibitor and blockage of the predicted ubiquinone binding site provide a model for the ‘deactive’ form of the enzyme. The proposed transition into the active form is based on a concerted structural rearrangement at the ubiquinone reduction site rendering support for a two-state stabilization-change mechanism of protonpumping.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44770
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-447702
SN  - 1095-9203
SN  - 0036-8075
N1  - Postprint, zuerst erschienen in: Science, 347.2015, Nr. 6217, S. 44-49, doi:10.1126/science.1259859
SP  - 1
EP  - 23
ER  -