Abstract
In humans the mitochondrial inner membrane protein Oxa1L is involved in the biogenesis of membrane proteins and facilitates the insertion of both mitochondrial- and nuclear-encoded proteins from the mitochondrial matrix into the inner membrane. The C-terminal approximately 100-amino acid tail of Oxa1L (Oxa1L-CTT) binds to mitochondrial ribosomes and plays a role in the co-translational insertion of mitochondria-synthesized proteins into the inner membrane. Contrary to suggestions made for yeast Oxa1p, our results indicate that the C-terminal tail of human Oxa1L does not form a coiled-coil helical structure in solution. The Oxa1L-CTT exists primarily as a monomer in solution but forms dimers and tetramers at high salt concentrations. The binding of Oxa1L-CTT to mitochondrial ribosomes is an enthalpy-driven process with a K(d) of 0.3-0.8 microM and a stoichiometry of 2. Oxa1L-CTT cross-links to mammalian mitochondrial homologs of the bacterial ribosomal proteins L13, L20, and L28 and to mammalian mitochondrial specific ribosomal proteins MRPL48, MRPL49, and MRPL51. Oxa1L-CTT does not cross-link to proteins decorating the conventional exit tunnel of the bacterial large ribosomal subunit (L22, L23, L24, and L29).
Highlights
Mammalian mitochondria synthesize 13 proteins, all of which are inserted into the respiratory chain complexes in the inner membrane
Contrary to suggestions made for yeast Oxa1p, our results indicate that the C-terminal tail of human Oxa1L does not form a coiled-coil helical structure in solution
Mammalian mitochondrial ribosomes are 55 S particles and have ϳ79 proteins, of which 42 have homologs in prokaryotic ribosomes, whereas 35 are specific for mitochondrial ribosomes. Twenty of these proteins have no clear homologs in yeast mitochondrial ribosomes [15], indicating a significant divergence between the protein composition of mitochondrial ribosomes from higher and lower eukaryotes. These differences may lead to significant alterations in the interaction of mitochondrial ribosomes from different sources with the machinery required for the insertion of mitochondrial translation products into the inner membrane
Summary
Mammalian mitochondria synthesize 13 proteins, all of which are inserted into the respiratory chain complexes in the inner membrane. In yeast several proteins play a role in this process including Oxa1p and Mba1 [3,4,5,6,7] Both of these proteins bind to yeast mitochondrial ribosomes and facilitate the insertion of mitochondrial translation products into the inner membrane. Genetic and biochemical studies indicate that the C-terminal tail binds to mitochondrial ribosomes and plays an important role in the insertion of newly synthesized mitochondrial polypeptides into the inner membrane [4]. Twenty of these proteins have no clear homologs in yeast mitochondrial ribosomes [15], indicating a significant divergence between the protein composition of mitochondrial ribosomes from higher and lower eukaryotes These differences may lead to significant alterations in the interaction of mitochondrial ribosomes from different sources with the machinery required for the insertion of mitochondrial translation products into the inner membrane. We have examined the structure of the C-terminal tail of human Oxa1L (Oxa1L-CTT) and analyzed its interaction with the mitochondrial ribosome
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