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Post-translational Modifications near the Quinone Binding Site of Mammalian Complex I

Complex I (NADH:ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 44 protein subunits with one arm buried in the inner membrane of the mitochondrion and the orthogonal arm protruding about 100 Å into the matrix. The protruding arm contains the binding sites for NADH, th...

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Autores principales: Carroll, Joe, Ding, Shujing, Fearnley, Ian M., Walker, John E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750175/
https://www.ncbi.nlm.nih.gov/pubmed/23836892
http://dx.doi.org/10.1074/jbc.M113.488106
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author Carroll, Joe
Ding, Shujing
Fearnley, Ian M.
Walker, John E.
author_facet Carroll, Joe
Ding, Shujing
Fearnley, Ian M.
Walker, John E.
author_sort Carroll, Joe
collection PubMed
description Complex I (NADH:ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 44 protein subunits with one arm buried in the inner membrane of the mitochondrion and the orthogonal arm protruding about 100 Å into the matrix. The protruding arm contains the binding sites for NADH, the primary acceptor of electrons flavin mononucleotide (FMN), and a chain of seven iron-sulfur clusters that carries the electrons one at a time from FMN to a coenzyme Q molecule bound in the vicinity of the junction between the two arms. In the structure of the closely related bacterial enzyme from Thermus thermophilus, the quinone is thought to bind in a tunnel that spans the interface between the two arms, with the quinone head group close to the terminal iron-sulfur cluster, N2. The tail of the bound quinone is thought to extend from the tunnel into the lipid bilayer. In the mammalian enzyme, it is likely that this tunnel involves three of the subunits of the complex, ND1, PSST, and the 49-kDa subunit. An arginine residue in the 49-kDa subunit is symmetrically dimethylated on the ω-N(G) and ω-N(G′) nitrogen atoms of the guanidino group and is likely to be close to cluster N2 and to influence its properties. Another arginine residue in the PSST subunit is hydroxylated and probably lies near to the quinone. Both modifications are conserved in mammalian enzymes, and the former is additionally conserved in Pichia pastoris and Paracoccus denitrificans, suggesting that they are functionally significant.
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spelling pubmed-37501752013-08-27 Post-translational Modifications near the Quinone Binding Site of Mammalian Complex I Carroll, Joe Ding, Shujing Fearnley, Ian M. Walker, John E. J Biol Chem Bioenergetics Complex I (NADH:ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 44 protein subunits with one arm buried in the inner membrane of the mitochondrion and the orthogonal arm protruding about 100 Å into the matrix. The protruding arm contains the binding sites for NADH, the primary acceptor of electrons flavin mononucleotide (FMN), and a chain of seven iron-sulfur clusters that carries the electrons one at a time from FMN to a coenzyme Q molecule bound in the vicinity of the junction between the two arms. In the structure of the closely related bacterial enzyme from Thermus thermophilus, the quinone is thought to bind in a tunnel that spans the interface between the two arms, with the quinone head group close to the terminal iron-sulfur cluster, N2. The tail of the bound quinone is thought to extend from the tunnel into the lipid bilayer. In the mammalian enzyme, it is likely that this tunnel involves three of the subunits of the complex, ND1, PSST, and the 49-kDa subunit. An arginine residue in the 49-kDa subunit is symmetrically dimethylated on the ω-N(G) and ω-N(G′) nitrogen atoms of the guanidino group and is likely to be close to cluster N2 and to influence its properties. Another arginine residue in the PSST subunit is hydroxylated and probably lies near to the quinone. Both modifications are conserved in mammalian enzymes, and the former is additionally conserved in Pichia pastoris and Paracoccus denitrificans, suggesting that they are functionally significant. American Society for Biochemistry and Molecular Biology 2013-08-23 2013-07-08 /pmc/articles/PMC3750175/ /pubmed/23836892 http://dx.doi.org/10.1074/jbc.M113.488106 Text en © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles
spellingShingle Bioenergetics
Carroll, Joe
Ding, Shujing
Fearnley, Ian M.
Walker, John E.
Post-translational Modifications near the Quinone Binding Site of Mammalian Complex I
title Post-translational Modifications near the Quinone Binding Site of Mammalian Complex I
title_full Post-translational Modifications near the Quinone Binding Site of Mammalian Complex I
title_fullStr Post-translational Modifications near the Quinone Binding Site of Mammalian Complex I
title_full_unstemmed Post-translational Modifications near the Quinone Binding Site of Mammalian Complex I
title_short Post-translational Modifications near the Quinone Binding Site of Mammalian Complex I
title_sort post-translational modifications near the quinone binding site of mammalian complex i
topic Bioenergetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750175/
https://www.ncbi.nlm.nih.gov/pubmed/23836892
http://dx.doi.org/10.1074/jbc.M113.488106
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