Seryl-tRNA Synthetase
Created by Jinga Kapanga
Seryl-tRNA synthetase is a protein that is classified as being in the aminoacyl-tRNA synthetase group1. These tRNA synthetases function as catalysts in the esterification of various amino acids1. These amino acids typically have a hydroxyl group that is located on the 3’-terminal adenosine of its respective cognate tRNA1. Most of these reactions require ATP and Mg2+ in order to form the active intermediate1. Seryl-tRNA synthetase can be divided into two groups within itself. The first group is described as being archeal/eukaryal2. The second group of seryl-tRNA synthetases can be classified as being a bacterial type2. However, between the two types of seryl-tRNA synthetases, they show very little sequence similarity, which is uncommon for most class II tRNA synthetases3.
Seryl-tRNA synthetase can bind to a large number of substrates to enable different functions. Different substrates have been added that have yielded significant results, such as binding a methanogenic compound such as Methamosarcina barkeri SeRs. By binding it to the seryl-tRNA synthetase, a Zn+ binding site was able to be found and is useful in serine ligation3. Seryl-tRNA synthetase should continue to be studied for various other reasons as well. For example, this protein has a significant interaction with ATP which is the main sources of energy in our system2.
The structure of this protein contains 455 amino acids and has two side chains that are not equal in length2. From these two side chains they form a helical arm that is joined by the extended chain1. The function of the helical arm is still being researched, but can be described as being an additional support of the anticodon stem1. Molecular weight of the structure is 106685.80 u 2. A distinct characterization that sets seryl-tRNA synthetase away from the other aminoacyl-tRNA synthetases is that it does not have a dinucleotide-binding fold1. Using software, it was determined that the isoelectric point of seryl-tRNA synthetase is 6.68.
Being a part of a classification of proteins makes it easier for seryl-tRNA synthetase to have homology with other proteins. This certain classification, outside of being a ligase, has a family of proteins that share similar structures and functions. Each protein in the classification, different in various ways, carries a characteristic similar to those of the some of the others. Some of the proteins that have significant homology with seryl-tRNA synthetase include proteins such as threonyl-tRNA synthetase and prolyl-tRNA synthetase1. These proteins are typically homologous with both side chains at various points1.
Threonyl-tRNA, with an ID of 1QF6, synthetase is one of the homologs of seryl-tRNA synthetase5. The similarities between the two sequences are both classified as ligases, but are also included in the aminoacyl-tRNA synthetase group5. Unlike seryl-tRNA synthetase, the threonyl-tRNA synthetase has only one α-side chain. The length of threonyl-tRNA synthetase is much larger than that of seryl-tRNA synthetase at 6425. The functions between the two tRNA synthetases do not vary in a large way. Each of the two synthetases requires ATP in order to activate them. Both are able to conform to different substrates in order to complete an enzymatic function. Threonyl-tRNA synthetase is also a catalyst for enzyme functions, but not for esterification as seryl-tRNA synthetase5. There are various everyday functions for both tRNA synthetases that occur on a daily basis within our systems.
Seryl-tRNA synthetase is a protein that is also a type-2 tRNA. It can be characterized by the long extra arm on its structure2. The length of the protein is 455 amino acids and also has two separate chains, an A and B chain2. Seryl-tRNA synthetase has two domains, or side chains. The first side chain, the alpha-chain, is made up of an anti-parallel coiled-coil of other alpha helices1. The beta side chain of seryl-tRNA synthetase however has a pleated sheet of eight different strands1.
Although there are eight strands in the beta-pleated sheet, it only comprises of 20% of the entire protein’s size1. The helical arm, or alpha chain, consists of two long anti-parallel helices1. These two helices are joined together by a short piece of the extended chain and make the two helices almost perpendicular to each other1. The arms each have different charges, the first of which has a negative charge and the second has a positive charge6.
The number of base pairs in the helix accounts for its ability to perform aminoacylation as well2. Stability of each of the side chains is also important to determining how well the protein functions. The alpha-helical chains are stabilized in three different ways1. It can be stabilized using inter-helical salt bridges and hydrogen bonds, or by using hydrophobic interactions, or even intra-helical hydrogen bonds1.
The globular domain, otherwise known as the beta domain, consists of a seven-stranded beta pleated sheet that has a parallel eighth strand1. There are also three short antiparallel beta sheet1. Two long helices are also attached, and one of which is perpendicular to the axis at the top of the protein molecule1. The other helix forms a “right handed cross-over connection” between two beta strands that are located outside of the sheet1. Within the globular domain, there is an archaea-specific insertion that is located in one corner of the domain2. The insertion is made of a two-stranded beta sheet and a short alpha helix2.
Seryl-tRNA synthetase can also be classified as a eukaryal synthetase. The structure of the eukaryal seryl-tRNA synthetase includes an extra arm in comparison to the bacterial seryl-tRNA synthetases7. These tRNAs that contain extra arms are split into two groups depending on the length of the arm. Type 1 tRNA synthetases have extra arms that have 4-5 nucleotides, while type 2 tRNA synthetases have extra arms of at least 11 nucleotides8. The extra arm of seryl-tRNA synthetase typically has a four base-pair stem4. The long arm determines the specificity of serylation8. A bacterial seryl-tRNA has more base-pairs than the eukaryal synthetase7.
Many of the tRNA synthetases vary in the N-terminal domain that is responsible for the recognition of the tRNA8. According to further research, the N-terminal helical domain of the seryl-tRNA synthetase protein is made up of a long anti-parallel coiled-coil and two N-terminal alpha helices2. It is also apparent that seryl-tRNA synthetases tend to bind across both subunits of the dimer8. Acceptors will bind to the active site of the subunit, and the rest of the seryl-tRNA synthetase is bound to the other subunit where the N-terminal helical arm is located8. This allows for the arm to recognize the long extra arm necessary for serylation8.
The structure of seryl-tRNA synthetase is extremely important to its function. By having an extra long arm which enable serylation, and to having two side chains, this protein is capable of various functions. Having two side chains allows for more diversity in its functions.