Thursday, January 6, 2011
How to swap a gearbox for a new model right on the highway
Protein biosyntheses is central a hub for cellular physiology: proteins are essencial for all the cellular processes. Therefore changing something really important in translational machinery is really hard: you still need to continue producing proteins! Swapping an important translational factor for another one? That sounds impossible, but this is exactly what happend with eEF1A - eukaryotic factor that brings aminoacylated tRNA to the ribosome. Moreover, it happened several times!
It was indeed swapped for a similar, yet different protein EFL (EF-Like) several times during eukaryotic evolution. The main difference between EFL and eEF1A is in theis GTPase cycle. eEF1A, just like its bacterial counterpart EF-Tu, needs a specialized factor in order to regenerate it from the GDP to GTP-bound state (Guanine nucleotide Exchange Factor, GEF). EFL does not need a GEF, so it is in a sense simpler.
Loosing a GEF seems to be a common theme in the evolution of translational GTPases. Mitochondrial EF-Tu lost its GEF (EF-Ts) in Saccharomyces cerevisiae, though retained that in human and S. pombe! Moreover, it is possible to select mutants in yeast eEF1A which would confere GEF-independence, turning into something like EFL.
Sometimes regulating GTPases is just too much to ask for and Nature cuts corners.
Keeling PJ, & Inagaki Y (2004). A class of eukaryotic GTPase with a punctate distribution suggesting multiple functional replacements of translation elongation factor 1alpha. Proceedings of the National Academy of Sciences of the United States of America, 101 (43), 15380-5 PMID: 15492217
Rosenthal LP, & Bodley JW (1987). Purification and characterization of Saccharomyces cerevisiae mitochondrial elongation factor Tu. The Journal of biological chemistry, 262 (23), 10955-9 PMID: 3301847
Chiron S, Suleau A, & Bonnefoy N (2005). Mitochondrial translation: elongation factor tu is essential in fission yeast and depends on an exchange factor conserved in humans but not in budding yeast. Genetics, 169 (4), 1891-901 PMID: 15695360
Ozturk SB, & Kinzy TG (2008). Guanine nucleotide exchange factor independence of the G-protein eEF1A through novel mutant forms and biochemical properties. The Journal of biological chemistry, 283 (34), 23244-53 PMID: 18562321