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Mdm38 is a 14-3-3-like receptor and associates with the protein synthesis machinery at the inner mitochondrial membrane

Mdm38 is a 14-3-3-like receptor and associates with the protein synthesis machinery at the inner mitochondrial membrane
Mdm38 is a 14-3-3-like receptor and associates with the protein synthesis machinery at the inner mitochondrial membrane
Mitochondrial ribosomes synthesize core subunits of the inner membrane respiratory chain complexes. In mitochondria, translation is regulated by mRNA-specific activator proteins and occurs on membrane-associated ribosomes. Mdm38/Letm1 is a conserved membrane receptor for mitochondrial ribosomes and specifically involved in respiratory chain biogenesis. In addition, Mdm38 and its higher eukaryotic homolog Letm1, function as K(+) /H(+) or Ca(2+) /H(+) antiporters in the inner membrane. Here, we identify the conserved ribosome-binding domain (RBD) of Mdm38 and determine the crystal structure at 2.1 Å resolution. Surprisingly, Mdm38(RBD) displays a 14-3-3-like fold despite any similarity to 14-3-3-proteins at the primary sequence level and thus represents the first 14-3-3-like protein in mitochondria. The 14-3-3-like domain is critical for respiratory chain assembly through regulation of Cox1 and Cytb translation. We show that this function can be spatially separated from the ion transport activity of the membrane integrated portion of Mdm38. On the basis of the phenotypes observed for mdm38? as compared to Mdm38 lacking the RBD, we suggest a model that combining ion transport and translational regulation into one molecule allows for direct coupling of ion flux across the inner membrane, and serves as a signal for the translation of mitochondrial membrane proteins via its direct association with the protein synthesis machinery.
14-3-3 protein, gene expression, letm1 homolog, mitochondria, respiratory chain biogenesis, ribosome
1398-9219
1457-1466
Lupo, Domenico
f9bed149-071d-4883-8fb2-370fed7e5f9c
Vollmer, Christine
15e43023-5667-491d-b749-f605dbe2b0fe
Deckers, Markus
f810d722-8d7d-4a31-b035-1fd398e90fa9
Mick, David U
65840174-2be1-4066-8485-f47315c141bf
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Sinning, Irmgard
fbc3f199-8a3b-47a6-9ee7-00bfc472e079
Rehling, Peter
3eab143f-2f9a-4a5b-9da9-a118eb937e5b
Lupo, Domenico
f9bed149-071d-4883-8fb2-370fed7e5f9c
Vollmer, Christine
15e43023-5667-491d-b749-f605dbe2b0fe
Deckers, Markus
f810d722-8d7d-4a31-b035-1fd398e90fa9
Mick, David U
65840174-2be1-4066-8485-f47315c141bf
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Sinning, Irmgard
fbc3f199-8a3b-47a6-9ee7-00bfc472e079
Rehling, Peter
3eab143f-2f9a-4a5b-9da9-a118eb937e5b

Lupo, Domenico, Vollmer, Christine, Deckers, Markus, Mick, David U, Tews, Ivo, Sinning, Irmgard and Rehling, Peter (2011) Mdm38 is a 14-3-3-like receptor and associates with the protein synthesis machinery at the inner mitochondrial membrane. Traffic, 12 (10), 1457-1466. (doi:10.1111/j.1600-0854.2011.01239.x). (PMID:21718401)

Record type: Article

Abstract

Mitochondrial ribosomes synthesize core subunits of the inner membrane respiratory chain complexes. In mitochondria, translation is regulated by mRNA-specific activator proteins and occurs on membrane-associated ribosomes. Mdm38/Letm1 is a conserved membrane receptor for mitochondrial ribosomes and specifically involved in respiratory chain biogenesis. In addition, Mdm38 and its higher eukaryotic homolog Letm1, function as K(+) /H(+) or Ca(2+) /H(+) antiporters in the inner membrane. Here, we identify the conserved ribosome-binding domain (RBD) of Mdm38 and determine the crystal structure at 2.1 Å resolution. Surprisingly, Mdm38(RBD) displays a 14-3-3-like fold despite any similarity to 14-3-3-proteins at the primary sequence level and thus represents the first 14-3-3-like protein in mitochondria. The 14-3-3-like domain is critical for respiratory chain assembly through regulation of Cox1 and Cytb translation. We show that this function can be spatially separated from the ion transport activity of the membrane integrated portion of Mdm38. On the basis of the phenotypes observed for mdm38? as compared to Mdm38 lacking the RBD, we suggest a model that combining ion transport and translational regulation into one molecule allows for direct coupling of ion flux across the inner membrane, and serves as a signal for the translation of mitochondrial membrane proteins via its direct association with the protein synthesis machinery.

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e-pub ahead of print date: 22 July 2011
Published date: October 2011
Keywords: 14-3-3 protein, gene expression, letm1 homolog, mitochondria, respiratory chain biogenesis, ribosome
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 200221
URI: http://eprints.soton.ac.uk/id/eprint/200221
ISSN: 1398-9219
PURE UUID: 1d9ac5fe-44cd-48c4-83da-396179fb6e0a
ORCID for Ivo Tews: ORCID iD orcid.org/0000-0002-4704-1139

Catalogue record

Date deposited: 24 Oct 2011 11:32
Last modified: 12 Nov 2019 01:41

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