Mechanistic insight from the crystal structure of mitochondrial complex I

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. I
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.
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Metadaten
Author:Volker Zickermann, Christophe Wirth, Hamid Reza Nasiri, Karin Siegmund, Harald Schwalbe, Carola Hunte, Ulrich Brandt
URN:urn:nbn:de:hebis:30:3-447702
DOI:http://dx.doi.org/10.1126/science.1259859
ISSN:1095-9203
ISSN:0036-8075
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25554780
Document Type:Article
Language:English
Date of Publication (online):2017/11/09
Year of first Publication:2015
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/11/09
Pagenumber:23
First Page:1
Last Page:23
Note:
Postprint, zuerst erschienen in: Science, 347.2015, Nr. 6217, S. 44-49, doi:10.1126/science.1259859
HeBIS PPN:432470689
Institutes:Medizin
Biochemie und Chemie
Exzellenzcluster Makromolekulare Komplexe
Sonderforschungsbereiche / Forschungskollegs
Zentrum für Biomolekulare Magnetische Resonanz (BMRZ)
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License Logo Veröffentlichungsvertrag für Publikationen

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