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
  
• (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
  
• (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
  
• (2018) Global collective motions in the mammalian and bacterial respiratory complex I. Biochim Biophys Acta Bioenerg 1859:326-332
  Di Luca A, Kaila VRI
  
• (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
  
• (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
  
• (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
  
• (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
  
• (2019) How cardiolipin modulates the structure and dynamics of respiratory complex I. Science Advances 5:eaav1850
  Jussupow A, Di Luca A, Kaila VRI
  
• (2019) Molekularen Mechanismen der biologischen Energieumwandlung. Nachr Chem 67
  Kaila VRI