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Literature summary for 2.1.1.220 extracted from
- m1A Post-transcriptional modification in tRNAs (2017), Biomolecules, 7, 20 .
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| crystal structure is available for heterotetrameric Trm6-Trm61A complex from Saccharomyces cerevisiae | Saccharomyces cerevisiae |
| crystal structure of the human m1A58 MTase in complex with tRNALys3 (PDB ID 5CCB), and of human complex Trm6-Trm61 (PDB ID 2B25) | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | two subunits Trm6-Trm61 | Saccharomyces cerevisiae | 5829 | - |
| cytosol | two subunits Trm6-Trm61 | Homo sapiens | 5829 | - |
| mitochondrion | only subunit Trm61 | Saccharomyces cerevisiae | 5739 | - |
| mitochondrion | only subunit Trm61 | Homo sapiens | 5739 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 2 S-adenosyl-L-methionine + adenine58 in tRNA | Thermus thermophilus | - |
2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA | - |
? |  |
| 2 S-adenosyl-L-methionine + adenine58 in tRNA | Saccharomyces cerevisiae | - |
2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA | - |
? | |
| 2 S-adenosyl-L-methionine + adenine58 in tRNA | Homo sapiens | - |
2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA | - |
? | |
| 2 S-adenosyl-L-methionine + adenine58 in tRNALys3 | Saccharomyces cerevisiae | - |
2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNALys3 | - |
? | |
| 2 S-adenosyl-L-methionine + adenine58 in tRNALys3 | Homo sapiens | - |
2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNALys3 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q9UJA5 AND Q96FX7 AND Q9BVS5 | subunits Trm6, Trm61A and Trm61B | - |
| Saccharomyces cerevisiae | P41814 AND P46959 | subunits Trm6 and Trm61,or GCD10 and GCD14, respectively | - |
| Thermus thermophilus | Q8GBB2 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 2 S-adenosyl-L-methionine + adenine58 in tRNA | - |
Thermus thermophilus | 2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA | - |
? | |
| 2 S-adenosyl-L-methionine + adenine58 in tRNA | - |
Saccharomyces cerevisiae | 2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA | - |
? | |
| 2 S-adenosyl-L-methionine + adenine58 in tRNA | - |
Homo sapiens | 2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA | - |
? | |
| 2 S-adenosyl-L-methionine + adenine58 in tRNALys3 | - |
Saccharomyces cerevisiae | 2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNALys3 | - |
? | |
| 2 S-adenosyl-L-methionine + adenine58 in tRNALys3 | - |
Homo sapiens | 2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNALys3 | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| heterotetramer | the eukaryotic complex of Trm6-Trm61 has been reported as a heterotetramer | Homo sapiens |
| heterotetramer | the eukaryotic complex of Trm6-Trm61 has been reported as a heterotetramer. In the complex of Trm6-Trm61 from Saccharomyces cerevisiae, both subunits harbour an N-terminal domain linked to a C-terminal domain. The C-terminal domains cover a Rossmann-fold and are very similar between the two subunits, whereas significant differences are found between the N-terminal domains. The N-terminal domain of Trm61 contains a short alpha-helix and three hairpin beta-motifs, whereas Trm6 consists of a short alpha-helix with seven antiparallel beta-strands and a highly flexible region with a number of positively-charged residues. Each subunit of the Trm6-Trm61 complex forms heterodimers that, again, assemble as a heterotetramer. The catalytic subunit of this complex (Trm61) binds the cofactor SAM, a binding that is made impossible in the other subunit (Trm6) by the loss of conserved motifs involved in accommodation of this cofactor. Each heterotetramer binds two tRNA molecules onto two distal, L-shaped surfaces on the protein complex | Saccharomyces cerevisiae |
| homotetramer | bacterial and archaeal TrmI proteins have been shown to form homotetramers. Each homotetramers accomodates up to two tRNA molecules | Thermus thermophilus |
| More | in mitochondria, MTase Trmt61B forms a tetramer, presumed to resemble the homotetramers of TrmI proteins. In support of a similar structural arrangement between Trmt61B and TrmI, a phylogenetic analysis confirmed a bacterial origin of the human protein | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| m1A58 MTase | - |
Thermus thermophilus |
| m1A58 MTase | - |
Saccharomyces cerevisiae |
| m1A58 MTase | - |
Homo sapiens |
| Trm6 | - |
Saccharomyces cerevisiae |
| Trm6 | - |
Homo sapiens |
| Trm61A | - |
Saccharomyces cerevisiae |
| Trm61A | - |
Homo sapiens |
| Trm61B | - |
Saccharomyces cerevisiae |
| Trm61B | - |
Homo sapiens |
| TrmI | - |
Thermus thermophilus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| S-adenosyl-L-methionine | - |
Thermus thermophilus | |
| S-adenosyl-L-methionine | - |
Saccharomyces cerevisiae | |
| S-adenosyl-L-methionine | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | the m1A58 modification occurs on (cyt)tRNAs from all three domains of life and further in (mt)tRNAs. The enzyme belongs to the RFM class I methyltransferases. In eukaryotes, the m1A58 MTase located in the cytosol is composed of a catalytic protein unit from the Trm61 subfamily (Trm61A) and an RNA-binding protein unit from the Trm6 subfamily (Trm6). Trm6 and Trm61 share a common ancestor and arose via gene duplication and divergent evolution. The mitochondrial m1A58 MTase consists of a single protein from the Trm61 family (Trmt61B), which is a paralogue to Trm61A from the cytosolic complex | Saccharomyces cerevisiae |
| evolution | the m1A58 modification occurs on (cyt)tRNAs from all three domains of life and further in (mt)tRNAs. The enzyme belongs to the RFM class I methyltransferases. In eukaryotes, the m1A58 MTase located in the cytosol is composed of a catalytic protein unit from the Trm61 subfamily (Trm61A) and an RNA-binding protein unit from the Trm6 subfamily (Trm6). Trm6 and Trm61 share a common ancestor and arose via gene duplication and divergent evolution. The mitochondrial m1A58 MTase consists of a single protein from the Trm61 family (Trmt61B), which is a paralogue to Trm61A from the cytosolic complex. In mitochondria, MTase Trmt61B forms a tetramer, presumed to resemble the homotetramers of TrmI proteins. In support of a similar structural arrangement between Trmt61B and TrmI, a phylogenetic analysis confirmed a bacterial origin of the human protein | Homo sapiens |
| evolution | the m1A58 modification occurs on (cyt)tRNAs from all three domains of life and further in (mt)tRNAs. The m1A58 MTases belong to the RFM methyltransferase superfamily, class I. In archaea and bacteria, the m1A58 MTases belong to the TrmI subfamily and function without complex partners | Thermus thermophilus |
| malfunction | deletion of the MTase N1-methylation A58 in yeast produces non-viable cells | Saccharomyces cerevisiae |
| malfunction | the lack of m1A58 in human tRNALys3 has been shown to be crucial for reverse transcription fidelity and efficiency of retroviruses like HIV-1. The lack of m1A58 results in an abnormal tRNAi structure, guiding it for degradation. This might explain why exclusion of this MTase by siRNA-mediated knockdown gives rise to a slow-growth phenotype in human cells | Homo sapiens |
| malfunction | the lack of the enzyme forming m1A58 leads to thermosensitivity in bacterial tRNAs | Thermus thermophilus |
| metabolism | in cytosolic (cyt) tRNA, the m1A modification occurs at five different positions (9, 14, 22, 57, and 58), two of which (9 and 58) are also found in mitochondrial (mt) tRNAs. In some cases, these modifications have been shown to increase tRNA structural stability and induce correct tRNA folding. Two enzyme families are responsible for formation of m1A at nucleotide position 9 and 58 in tRNA, tRNA binding, m1A mechanism, protein domain organisation and overall structures | Homo sapiens |
| metabolism | in cytosolic (cyt) tRNA, the m1A modification occurs at five different positions (9, 14, 22, 57, and 58), two of which (9 and 58) are also found in mitochondrial tRNAs. In some cases, these modifications have been shown to increase tRNA structural stability and induce correct tRNA folding. Two enzyme families are responsible for formation of m1A at nucleotide position 9 and 58 in tRNA, tRNA binding, m1A mechanism, protein domain organisation and overall structures | Saccharomyces cerevisiae |
| additional information | catalytic mechanism of m1A58 specific RFM family member TrmI, overview. The conserved aspartate residue (Asp181) is essential for m1A58 MTase activity in Thermus thermophilus | Thermus thermophilus |
| additional information | crystal structure of the human m1A58 MTase in complex with tRNALys3 have not provided information on the correct mechanism, as the position of A58 in the active site resembles a methylated nucleobase in a product-complex | Homo sapiens |
| additional information | crystal structure of the human m1A58 MTase in complex with tRNALys3 have not provided information on the correct mechanism, as the position of A58 in the active site resembles a methylated nucleobase in a product-complex. tRNA undergoes large conformational changes during binding in which the D- and T-arm are separated. The T-loop contains the nucleobase to be modified (A58) and binds in the active site. The binding is stabilised by the formation of numerous hydrogen bonds with the C56 nucleobase and the sugar-phosphate backbone. A stabilising hydrogen bond is also formed between a phosphate O atom of C56 and a H atom of the exocyclic N6 atom of A58. No hydrogen bonds are observed between the protein complex and A58, and the orientation of this adenosine towards the bound S-adenosyl-L-homocysteine (SAH) resembles a methylated nucleobase. A conserved aspartate residue (Asp181) is found in close proximity to A58 and could serve as the catalytic base. The complex makes additional contacts with the tRNA substrate with binding of the acceptor stem to the N?terminal domain of the catalytic subunit Trm61, and binding of the T?stem/loop to an insert in the N?terminal domain of Trm6, not present in Trm61. The vast number of interactions with both complex subunits explain previous findings that both Trm6 and Trm61 are required for tRNA binding. The interactions between tRNA and Trm6 help orient A58 for catalysis and may contribute to target specificity, providing a role for the non?catalytic subunit Trm6 in activity | Saccharomyces cerevisiae |
| physiological function | the m1A58 modifications have both been linked to structural stability and/or correct folding of the tRNA and is related to structural thermostability of tRNA, role of m1A58 in tRNAi structure stability. m1A58 is important for maturation of the initiator tRNAMet from yeast. The initiator tRNA from eukaryotes (tRNAi) has a conserved A-rich T-loop (A54, A58, and A69), a conserved A20 and a shorter-than-average D-loop (seven nucleobases). These features cluster in the corner of the L-shaped tRNA and the structure is maintained by a dense network of hydrogen bonds between the conserved adenines. In this network, A58 forms hydrogen bonds to A54 and A60 | Saccharomyces cerevisiae |
| physiological function | the m1A58 modifications have both been linked to structural stability and/or correct folding of the tRNA and is related to structural thermostability of tRNA, role of m1A58 in tRNAi structure stability. The initiator tRNA from eukaryotes (tRNAi) has a conserved A-rich T-loop (A54, A58, and A69), a conserved A20 and a shorter-than-average D-loop (seven nucleobases). These features cluster in the corner of the L-shaped tRNA and the structure is maintained by a dense network f hydrogen bonds between the conserved adenines. In this network, A58 forms hydrogen bonds to A54 and A60 | Homo sapiens |
| physiological function | the m1A58 modifications have both been linked to structural stability and/or correct folding of the tRNA and is related to structural thermostability of tRNA. The combination of m1A58 with two other post-transcriptional modifications (Gm18 and m5s2U54) increases the melting temperature of tRNAs from Thermus thermophilus by approximately 10°C compared to the unmodified transcript | Thermus thermophilus |
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Release 2023.1 (January 2023)
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