The role of a conserved tyrosine in the 49-kDa subunit of complex I for ubiquinone binding and reduction

Biochimica Et Biophysica Acta
Maja A TocilescuUlrich Brandt

Abstract

Iron-sulfur cluster N2 of complex I (proton pumping NADH:quinone oxidoreductase) is the immediate electron donor to ubiquinone. At a distance of only approximately 7A in the 49-kDa subunit, a highly conserved tyrosine is found at the bottom of the previously characterized quinone binding pocket. To get insight into the function of this residue, we have exchanged it for six different amino acids in complex I from Yarrowia lipolytica. Mitochondrial membranes from all six mutants contained fully assembled complex I that exhibited very low dNADH:ubiquinone oxidoreductase activities with n-decylubiquinone. With the most conservative exchange Y144F, no alteration in the electron paramagnetic resonance spectra of complex I was detectable. Remarkably, high dNADH:ubiquinone oxidoreductase activities were observed with ubiquinones Q1 and Q2 that were coupled to proton pumping. Apparent Km values for Q1 and Q2 were markedly increased and we found pronounced resistance to the complex I inhibitors decyl-quinazoline-amine (DQA) and rotenone. We conclude that Y144 directly binds the head group of ubiquinone, most likely via a hydrogen bond between the aromatic hydroxyl and the ubiquinone carbonyl. This places the substrate in an ideal distanc...Continue Reading

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Citations

Mar 27, 2013·Annual Review of Biochemistry·Judy Hirst
Aug 1, 2014·Journal of Bioenergetics and Biomembranes·Eiko Nakamaru-OgisoJoseph A Sakyiama
Jan 2, 2016·Biochimica Et Biophysica Acta·Judy Hirst, Maxie M Roessler
Feb 28, 2016·Biochimica Et Biophysica Acta·Christophe WirthVolker Zickermann
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Apr 10, 2012·Biochimica Et Biophysica Acta·Heike AngererUlrich Brandt
May 15, 2012·Biochimica Et Biophysica Acta·Michael VerkhovskyMarina Verkhovskaya
May 14, 2011·Biochimica Et Biophysica Acta·Ulrich Brandt
May 25, 2010·Biochimica Et Biophysica Acta·Maja A TocilescuUlrich Brandt
Apr 15, 2015·Biochimica Et Biophysica Acta·Madhavan NarayananEiko Nakamaru-Ogiso
Sep 18, 2012·The International Journal of Biochemistry & Cell Biology·Marina Verkhovskaya, Dmitry A Bloch
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Jan 8, 2021·Parasitology·Petra ČermákováAnton Horváth
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Jun 13, 2020·Biochimica Et Biophysica Acta. Bioenergetics·Umesh KhaniyaM R Gunner
Apr 17, 2018·Biochimica Et Biophysica Acta. Bioenergetics·Outi Haapanen, Vivek Sharma
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