Molecular Mechanisms of Energy Conversion in Respiratory Complex I

• Applicant: Professor Dr. Ville Kaila
• Subject Area: Theoretical Chemistry: Electronic Structure, Dynamics, Simulation ; Biochemistry ; Biophysics
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277706513

• Final Report Year: 2021

Final Report Abstract

In this project, we first developed simulation models of the bacterial respiratory Complex I based on a crystal structure at 3.3 Å resolution. These simulations allowed us to study how quinone (Q) reduction results in structural and dynamical changes and how, in turn, these could activate the proton-pump, and provided a starting point for simulations on other Complex I variants. We addressed the energetics of proton transfer though the membrane subunits, and electron transfer linked to Q reduction in the soluble domain of Complex I. The project was highly successful and resulted in several peer-reviewed publications, published in excellent journals including PNAS, JACS, and Science Advances.

Publications

• (2015) Redox-Induced Activation of the Proton Pump in the Respiratory Complex I. Proc Natl Acad Sci USA 112:11571-11576
  Sharma V, Belevich G, Gamiz-Hernandez AP, Rog T, Vattulainen I, Wikström M, Hummer G, Kaila VRI
  (See online at https://doi.org/10.1073/pnas.1503761112)
• (2017) Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I. Proc Natl Acad Sci USA 114:12737-12742
  Fedor JG, Jones AJY, Di Luca A, Kaila VRI, Hirst J
  (See online at https://doi.org/10.1073/pnas.1714074114)
• (2017) Symmetry related proton transfer pathways in respiratory complex I. Proc Natl Acad Sci USA 114:E6314-E6321
  Di Luca A, Gamiz-Hernandez AP, Kaila VRI
  (See online at https://doi.org/10.1073/pnas.1706278114)
• (2018) Global collective motions in the mammalian and bacterial respiratory complex I. Biochim Biophys Acta Bioenerg 1859:326-332
  Di Luca A, Kaila VRI
  (See online at https://doi.org/10.1016/j.bbabio.2018.02.001)
• (2018) How inter-subunit contacts in the membrane domain of complex I affect proton transfer energetics. Biochim Biophys Acta Bioenerg 1859:734-741
  Di Luca A, Mühlbauer M, Saura P, Kaila VRI
  (See online at https://doi.org/10.1016/j.bbabio.2018.06.001)
• (2018) Long-Range Proton-Coupled Electron Transfer in Biological Energy Conversion: Towards Mechanistic Understanding of Respiratory Complex I. J. R. Soc. Interfaces 15: 20170916
  Kaila VRI
  (See online at https://doi.org/10.1098/rsif.2017.0916)
• (2018) Multi-scale Molecular Simulations on Respiratory Complex I. in ChemicalBiology No. 5, "Mechanisms of Primary Energy Transduction in Biology", Ed. Mårten Wikström, The Royal Society of Chemistry 2018
  Kaila VRI
  (See online at https://doi.org/10.1039/9781788010405-00081)
• (2018) Redox-coupled quinone dynamics in the respiratory complex I. Proc Natl Acad Sci USA 115:E8413-E8420
  Warnau J, Sharma V, Gamiz-Hernandez AP, Di Luca A, Haapanen O, Vattulainen I, Wikström M, Hummer G, Kaila VRI
  (See online at https://doi.org/10.1073/pnas.1805468115)
• (2019) How cardiolipin modulates the structure and dynamics of respiratory complex I. Science Advances 5:eaav1850
  Jussupow A, Di Luca A, Kaila VRI
  (See online at https://doi.org/10.1126/sciadv.aav1850)
• (2019) Molekularen Mechanismen der biologischen Energieumwandlung. Nachr Chem 67
  Kaila VRI
  (See online at https://doi.org/10.1002/nadc.20194092115)