Mitochondrial ribosomes synthesise core subunits of the inner membranerespiratory chain complexes. In mitochondria, ribosomes are mainly membraneassociated and translation is tightly coupled to the inner mitochondrialmembrane. Mdm38/Letm1 is a conserved membrane receptor for mitochondrialribosomes and specifically involved in respiratory chain biogenesis.These proteins play a role in potassium and hydrogen ion exchange [, ]. Some features found in LETM1, such as a transmembrane domain and a CK2 and PKC phosphorylation site [], are relatively conserved throughout the family. Deletion of LETM1 is thought to be involved in the development of Wolf-Hirschhorn syndrome in humans [].This entry represents the Letm1 ribosome-binding domain (RBD) of Letm1 from animals and MDM38 from yeast. This domain is necessary and sufficient forinteraction with mitochondrial ribosomes. It exhibits a predominantly α-helical compact fold and contains extended, highly chargedsurface patches. The conserved regions most probably represent interactionsites for ribosomal RNA or protein subunits, or for proteins involved inmitochondrial protein biogenesis [, ].
This family represents a group of LETM1-like mitochondrial inner membrane proteins, including LETM1/LETM2 from mammals and YLH47/MDM38 from yeastsLETM1 is a proton/calcium antiporter that mediates proton-dependent calcium efflux from mitochondrion []. LETM2 is preferentially expressed in testis and sperm. In humans, deletion of LETM1 causes Wolf-Hirschhorn syndrome []. MDM38 is involved in potassium homeostasis []and, with MBA1, it plays a role in ribosomal translation and protein insertion into the inner membrane [].
