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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    ABSTRACT: The aryl-hydrocarbon receptor (AHR), a ligand activated PAS superfamily transcription factor, mediates most, if not all, of the toxicity induced upon exposure to various dioxins, dibenzofurans, and planar polyhalogenated biphenyls. While AHR-mediated gene regulation plays a central role in the toxic response to dioxin exposure, a comprehensive understanding of AHR biology remains elusive. AHR-mediated signaling starts in the cytoplasm, where the receptor can be found in a complex with the heat shock protein of 90 kDa (Hsp90) and the immunophilin-like protein, aryl-hydrocarbon receptor-interacting protein (AIP). The role these chaperones and other putative interactors of the AHR play in the toxic response is not known. To more comprehensively define the AHR-protein interaction network (AHR-PIN) and identify other potential pathways involved in the toxic response, a proteomic approach was undertaken. Using tandem affinity purification (TAP) and mass spectrometry we have identified several novel protein interactions with the AHR. These interactions physically link the AHR to proteins involved in the immune and cellular stress responses, gene regulation not mediated directly via the traditional AHR:ARNT heterodimer, and mitochondrial function. This new insight into the AHR signaling network identifies possible secondary signaling pathways involved in xenobiotic-induced toxicity.
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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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    ABSTRACT: Mitochondrial ribosomal protein 20 (Mrp20) is a component of the yeast mitochondrial large (54S) ribosomal subunit and is homologous to the bacterial L23 protein, located at the ribosomal tunnel exit site. The carboxy-terminal mitochondrial-specific domain of Mrp20 was found to have a crucial role in the assembly of the ribosomes. A new, membrane-bound, ribosomal-assembly subcomplex composed of known tunnel-exit-site proteins, an uncharacterized ribosomal protein, MrpL25, and the mitochondrial peroxiredoxin (Prx), Prx1, accumulates in an mrp20ΔC yeast mutant. Finally, data supporting the idea that the inner mitochondrial membrane acts as a platform for the ribosome assembly process are discussed.
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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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