The interaction of mammalian mitochondrial translational initiation factor 3 with ribosomes: evolution of terminal extensions in IF3 sub(mt)

• Published in: Nucleic acids research Vol. 36; no. 2; pp. 589 - 597
• Main Authors: Haque, MdEmdadul, Grasso, Domenick, Spremulli, Linda L
• Format: Journal Article
• Language: English
• Published: 01-02-2008
• ISSN: 0305-1048; 1362-4962

Mammalian mitochondrial initiation factor 3 (IF3 sub(mt)) has a central region with homology to bacterial IF3. This homology region is preceded by an N-terminal extension and followed by a C-terminal extension. The role of these extensions on the binding of IF3 sub(mt) to mitochondrial small ribosomal subunits (28S) was studied using derivatives in which the extensions had been deleted. The K sub(d) for the binding of IF3 sub(mt) to 28S subunits is similar to 30 nM. Removal of either the N- or C-terminal extension has almost no effect on this value. IF3 sub(mt) has very weak interactions with the large subunit of the mitochondrial ribosome (39S) (K sub(d) = 1.5 mu M). However, deletion of the extensions results in derivatives with significant affinity for 39S subunits (K sub(d) = 0.12-0.25 mu M). IF3 sub(mt) does not bind 55S monosomes, while the deletion derivative binds slightly to these particles. IF3 sub(mt) is very effective in dissociating 55S ribosomes. Removal of the N-terminal extension has little effect on this activity. However, removal of the C-terminal extension leads to a complex dissociation pattern due to the high affinity of this derivative for 39S subunits. These data suggest that the extensions have evolved to ensure the proper dissociation of IF3 sub(mt) from the 28S subunits upon 39S subunit joining.