Mammalian mitochondrial ribosomal proteins (4) - Amino acid sequencing, characterization, and identification of corresponding gene sequences

Mitochondrial ribosomal proteins (MRPs) are required for the translation of all 13 mitochondrial encoded genes in humans. It has been speculated that mutations and polymorphisms in the human MRPs may be a primary cause of som e oxidative phosphorylation disorders or modulate the severity and tissue s pecificity of pathogenic mitochondrial DNA mutations. Although the sequence s of most of the yeast MRPs are known, only very few mammalian and nearly n o human MRPs have been completely characterized, MRPs differ greatly in seq uence, and sometimes biochemical properties, between different species, not allowing easy recognition by sequence homology, Therefore, the Mammalian M itochondrial Ribosomal Consortium is using a direct approach of purifying i ndividual mammalian (bovine) MRPs, determining their N-terminal and/or inte rnal peptide sequences using different protein sequencing techniques, and u sing the resulting sequence information for screening expressed sequence ta gs and genomic data bases to determine human, mouse, and rat homologues of the bovine proteins, Two proteins of the large and three proteins of the sm all ribosomal subunit have been analyzed in this manner, Three of them repr esent "new," i.e. formerly unknown mammalian mitochondrial ribosomal protei n classes. Only one of these three different MRPs shows significant sequenc e similarities to known ribosomal proteins. In one case, the corresponding human genomic DNA sequences were found in the data bases, and the exon/intr on structure was determined.