3IAS

Crystal structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus, oxidized, 4 mol/ASU, re-refined to 3.15 angstrom resolution

Summary for 3IAS

• Entry DOI: 10.2210/pdb3ias/pdb
• Related: 2FUG 3I9V 3IAM
• Descriptor: NADH-quinone oxidoreductase subunit 1, FLAVIN MONONUCLEOTIDE, FE2/S2 (INORGANIC) CLUSTER, ... (12 entities in total)
• Functional Keywords: oxidoreductase, electron transport, respiratory chain
• Biological source: Thermus thermophilus; More
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: Q56222 Q56221 Q56223 Q56220 Q56219 Q56218 Q56224 Q5SKZ7
• Total number of polymer chains: 32
• Total formula weight: 1138364.34

Authors

Sazanov, L.A.,Berrisford, J.M. (deposition date: 2009-07-14, release date: 2009-09-15, Last modification date: 2023-09-06)

Primary citation

Berrisford, J.M.,Sazanov, L.A.
Structural basis for the mechanism of respiratory complex I
J.Biol.Chem., 284:29773-29783, 2009

PubMed Abstract: Complex I plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. The mechanism of this highly efficient enzyme is currently unknown. Mitochondrial complex I is a major source of reactive oxygen species, which may be one of the causes of aging. Dysfunction of complex I is implicated in many human neurodegenerative diseases. We have determined several x-ray structures of the oxidized and reduced hydrophilic domain of complex I from Thermus thermophilus at up to 3.1 A resolution. The structures reveal the mode of interaction of complex I with NADH, explaining known kinetic data and providing implications for the mechanism of reactive oxygen species production at the flavin site of complex I. Bound metals were identified in the channel at the interface with the frataxin-like subunit Nqo15, indicating possible iron-binding sites. Conformational changes upon reduction of the complex involve adjustments in the nucleotide-binding pocket, as well as small but significant shifts of several alpha-helices at the interface with the membrane domain. These shifts are likely to be driven by the reduction of nearby iron-sulfur clusters N2 and N6a/b. Cluster N2 is the electron donor to quinone and is coordinated by unique motif involving two consecutive (tandem) cysteines. An unprecedented "on/off switch" (disconnection) of coordinating bonds between the tandem cysteines and this cluster was observed upon reduction. Comparison of the structures suggests a novel mechanism of coupling between electron transfer and proton translocation, combining conformational changes and protonation/deprotonation of tandem cysteines.

PubMed: 19635800
DOI: 10.1074/jbc.M109.032144

Experimental method

X-RAY DIFFRACTION (3.15 Å)