Journal: Mol Cell / Year: 2019 Title: Structures of Respiratory Supercomplex I+III Reveal Functional and Conformational Crosstalk. Authors: James A Letts / Karol Fiedorczuk / Gianluca Degliesposti / Mark Skehel / Leonid A Sazanov / Abstract: The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We ...The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII. CI shows a transition between "closed" and "open" conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII, suggesting that interaction with CI disrupts CIII symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.
History
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Deposition site: PDBE / Processing site: PDBE
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Revision 1.1
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Average exposure time: 2 sec. / Electron dose: 51 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1854
Image scans
Movie frames/image: 34
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Processing
EM software
ID
Name
Version
Category
1
RELION
2
particleselection
2
EPU
imageacquisition
4
Gctf
CTFcorrection
7
Coot
0.8.9
modelfitting
9
PHENIX
1.13-2998
modelrefinement
10
RELION
2
initialEulerassignment
11
RELION
2
finalEulerassignment
12
RELION
2
classification
13
RELION
2
3Dreconstruction
CTF correction
Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selection
Num. of particles selected: 400000
Symmetry
Point symmetry: C1 (asymmetric)
3D reconstruction
Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 35640 / Num. of class averages: 1 / Symmetry type: POINT
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