Mapping of the Saccharomyces cerevisiae Oxa1-Mitochondrial Ribosome Interface and Identification of MrpL40, a Ribosomal Protein in Close Proximity to Oxa1 and Critical for Oxidative Phosphorylation Complex Assembly

Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin 53233, USA.
Eukaryotic Cell (Impact Factor: 3.18). 09/2009; 8(11):1792-802. DOI: 10.1128/EC.00219-09
Source: PubMed


The Oxa1 protein plays a central role in facilitating the cotranslational insertion of the nascent polypeptide chains into
the mitochondrial inner membrane. Mitochondrially encoded proteins are synthesized on matrix-localized ribosomes which are
tethered to the inner membrane and in physical association with the Oxa1 protein. In the present study we used a chemical
cross-linking approach to map the Saccharomyces cerevisiae Oxa1-ribosome interface, and we demonstrate here a close association of Oxa1 and the large ribosomal subunit protein, MrpL40.
Evidence to indicate that a close physical and functional relationship exists between MrpL40 and another large ribosomal protein,
the Mrp20/L23 protein, is also provided. MrpL40 shares sequence features with the bacterial ribosomal protein L24, which like
Mrp20/L23 is known to be located adjacent to the ribosomal polypeptide exit site. We propose therefore that MrpL40 represents
the Saccharomyces cerevisiae L24 homolog. MrpL40, like many mitochondrial ribosomal proteins, contains a C-terminal extension region that bears no similarity
to the bacterial counterpart. We show that this C-terminal mitochondria-specific region is important for MrpL40's ability
to support the synthesis of the correct complement of mitochondrially encoded proteins and their subsequent assembly into
oxidative phosphorylation complexes.

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    • "One protein, Mrpl40, was also identified in the 30- and 240-minute TCDD treatment samples. In yeast, this protein has been shown to play a role in growth rate, mitochondrial protein folding, and mitochondrial function [34, 35]. In humans, the Mrpl40 gene is part of a chromosomal deletion of 22q11 in velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome [36, 37]. "
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    • "Previous work using chemical crosslinking approaches has identified a network of proteins—Mrp20, MrpL4, MrpL40, MrpL27, MrpL22, MrpL13 and MrpL3—that are located near to the exit site of the polypeptide tunnel of the 54S particle in yeast (Jia et al, 2009; Gruschke et al, 2010). This network includes contact points for the association of the ribosomes with components of the inner membrane, Oxa1 and Mba1, that are involved with the membrane insertion of nascent chains (Jia et al, 2003, 2009; Ott et al, 2006; Gruschke et al, 2010). "
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    • "This protein seems also to be involved in Ca 2+ transport [54]. Yeast Oxa1 protein, which facilitates the cotranslational insertion of the nascent polypeptide chains into the mitochondrial inner membrane, is closely associated to the large ribosomal subunit protein, MrpL40 [22]. It should also be mentioned that translational activator proteins in yeast are integral membrane proteins or bound to the mitochondrial inner membrane. "
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