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Structural Studies of Respirasome by Cryo-Electron Microscopy
Applied Microscopy 2018;48:81-6
Published online December 28, 2018
© 2018 Korean Society of Microscopy.

Tae Jin Jeon, Ho Min Kim1, and Seong Eon Ryu*

Department of Bioengineering, College of Engineering, Hanyang University, Seoul 04763, Korea, 1Graduate School of Medical Science & Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
Correspondence to: Ryu SE, http://orcid.org/0000-0003-3335-326X, Tel: +82-2-2220-4020, Fax: +82-2-2220-4023, E-mail: ryuse@hanyang.ac.kr
Received October 25, 2018; Revised November 21, 2018; Accepted November 22, 2018.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

The respiratory chain complex forms a supercomplex (SC) in the inner mitochondrial membrane. This complex facilitates the process of electron transfer to produce the proton gradient used to synthesize ATP. Understanding the precise structure of the SC is considered an important challenge. However, it has not yet been reported. The development of a Cryo-electron microscopy (EM) technique provides an effective way to obtain high-resolution micrographs to determine the high-resolution three-dimensional structure of biomolecules. In this brief review, the currently reported Cryo-EM structures of the mammalian respirasome have been described in order to establish a direction for further research in the respiratory system.

Keywords : Cryo-electron microscopy, Biomolecule structure, Respiratory chain complex, Respirasome
Figures
Fig. 1. Cryo-electron microscopy (EM) structure of mammalian supercomplex (SC) I1III2IV1 and CI. (A) The Cryo-EM structure of the porcine SC I1III2IV1 (upper row, PDB code 5GUP) and the EM density map (bottom row, EMD-9539) (). The map corresponding to porcine SC was generated from the 4.0 Å map at a contour level of 0.0412 using the UCSF chimera (). Top views are from the matrix (left) and side views along the membrane (right). CI, CIII, and CIV are colored in green, light blue, and light pink, respectively. The transmembrane region is indicated by two curved lines. IM, inner membrane; IMS, intermembrane space; CI, complex I; CIII, complex III; CIV, complex IV. (B) Cartoon representation of tight (left, PDB code 5J4Z) and loose SC (right, PDB code 5J7Y) from ovine samples are shown viewed from the top view (). CIV is shown in the red dashed circle. (C) Cartoon representation of the 3.9 Å resolution structure of the ovine CI (PDB code 5LNK). The core and extra subunits are colored (). The 14 core-subunits and 31 supernumerary subunits are colored in light magenta and cyan, respectively.
Fig. 2. Two proposed mechanisms of electron transfer. Symmetric (A) and asymmetric electron flow (B) through CIII are shown. Ubiquinol trail from CI to CIII is shown as a black thick line. The electron trail and transport of protons are shown as a black line. The hemes and FeS clusters are shown as spheres and the ubiquinol molecule are shown as sticks in the red oval. The ubiquinone binding site is shown in the blue dashed circle. The transmembrane region is indicated by two curved lines. The proximal and distal domains of CIII are colored in cyan and yellow, respectively. The CI and CIV are colored in magenta and grey, respectively. CI, complex I; CIII, complex III; CIV, complex IV.
Tables

Structures of respiratory supercomplex

PDB code State Species Method Resolution (Å) Author
2YBB I1III2IV1 Bovine EM 19.0 (Althoff et al., 2011)
5J4Z I1III2IV1 (tight) Ovine EM 5.8 (Letts et al., 2016)
5J7Y I1III2IV1 (loose) 6.7
5GPN I1III2IV1 Porcine EM 5.4 (Gu et al., 2016)
5GUP I1III2IV1 Porcine EM 4.0 (Wu et al., 2016)
5LUF I1III2IV1 Bovine EM 9.1 (Sousa et al., 2016)
5XTH I1III2IV1 Human EM 3.9 (Guo et al., 2017)
5XTI I2III2IV2 17.4

EM, electron microscopy.


Structures of respiratory complex I

PDB code State Species Method Resolution (Å) Author
3M9S N/A Thermus thermophilus X-ray 4.5 (Efremov et al., 2010)
4HEA N/A T. thermophilus X-ray 3.3 (Baradaran et al., 2013)
4UQ8 N/A Bovine EM 4.95 (Vinothkumar et al., 2014)
4WZ7 Deactive Yarrowia lipolytica X-ray 3.6 (Zickermann et al., 2015)
5LC5 Active Bovine EM 4.35 (Zhu et al., 2016)
5LDW Deactive 4.27
5LDX N/A 5.6
5LNK Deactive Ovine EM 3.9 (Fiedorczuk et al., 2016)
5O31 Deactive Bovine EM 4.13 (Blaza et al., 2018)
6G2J Active Mouse EM 3.3 (Agip et al., 2018)
6G72 Deactive 3.9
6GCS Deactive Y. lipolytica EM 4.32 (Parey et al., 2018)

N/A, not applicable; EM, electron microscopy.


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