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The family of mitochondrial transport proteins

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Mitochondrial transport proteins translocate nucleotides, amino acids, inorganic ions, fatty acids, keto acids and cofactors across the inner membrane of mitochondria. These transport steps are required for the generation of ATP from the oxidation of sugars and fat; the breakdown, synthesis and inter-conversion of amino acids; the synthesis of haem and iron sulphur clusters; heat production; and macromolecular synthesis in the mitochondrion. Dysfunctional transport proteins are associated with rare but severe human diseases, such as metabolic disorders and muscular and neurodegenerative diseases. The transport proteins share several sequence features, including a signature motif PX[DE]XX[RK] and three homologous amino acid sequence repeats. Their structural folds consist of six transmembrane -helices and three matrix -helices that are arranged with threefold pseudo-symmetry in agreement with the sequence repeats. The central cavity contains a single substrate binding site flanked by two conserved and symmetrical triplets of positively and negatively charged residues that have the propensity to form salt bridge networks. During the transport cycle the disruption and formation of two salt bridge networks are coupled to the opening and closing of the transport protein on either side of the mitochondrial inner membrane in an alternating fashion.

This talk is part of the Genetics Seminar Series series.

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