Thymidine kinase 1 regulatory fine-tuning through tetramer formation.
Thymidine kinase 1 (TK1) provides a crucial precursor, deoxythymidine monophosphate, for nucleic acid synthesis, and the activity of TK1 increases by up to 200-fold during the S-phase of cell division in humans. An important part of the regulatory checkpoints is the ATP and enzyme concentration-dependent transition of TK1 from a dimer with low catalytic efficiency to a tetramer with high catalytic efficiency. This regulatory fine-tuning serves as an additional control to provide a balanced pool of nucleic acid precursors in the cell. We subcloned and over-expressed 10 different TK1s, originating from widely different organisms, and characterized their kinetic and oligomerization properties. Whilst bacteria, plants and Dictyostelium only exhibited dimeric TK1, we found that all animals had a tetrameric TK1. However, a clear ATP-dependent switch between dimer and tetramer was found only in higher vertebrates and was especially pronounced in mammalian and bird TK1s. We suggest that the dimer form is the original form and that the tetramer originated in the animal lineage after the split of Dictyostelium and the lineages leading to invertebrates and vertebrates. The efficient switching mechanism was probably first established in warm-blooded animals when they separated from the rest of the vertebrates.
Department of Biology, Lund University, Lund, Sweden. Zeeshan.Mutahir@biol.lu.se
Zeeshan
Z
Mutahir
Anders R
AR
Clausen
Karl-Magnus
KM
Andersson
Sofia M
SM
Wisen
Birgitte
B
Munch-Petersen
Jure
J
Piškur
D000255:Adenosine Triphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics; D001409:Bacillus cereus / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D004023:Dictyostelium / Q000201:enzymology / Q000235:genetics; D057075:Enzyme Assays; D019143:Evolution, Molecular; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics; D006801:Humans; D016366:Open Reading Frames; D010802:Phylogeny; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013937:Thymidine Kinase / Q000737:chemistry* / Q000235:genetics
D001426:Bacterial Proteins; D010940:Plant Proteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D013937:Thymidine Kinase; C092717:thymidine kinase 1