Arsenite resistance protein

From Proteopedia

Function

Arsenite Resistance Protein (ARS2), otherwise known as the Serrate RNA effector molecule homolog, is a protein that is found in many species. The ARS2 being observed today, however, is from humans. It is produced by the SRRT gene [5]. ARS2 was originally discovered because of its ability to provide arsenic resistance in organisms. The first of its kind was found in plants (such as Arabidopsis thaliana), but since has been discovered in Drosophila and, in this case, humans. In Drosophila and other metazoans, ARS2 was found to have another purpose besides arsenic resistance. It was also found to help with RNA [4]. It can be used, in conjunction with other proteins (such as the cap-binding complex, CBC) to form a multiprotein complex. ARS2 serves as the mediator between this complex and micro-RNA (miRNA), which binds to DNA to silence gene expression [5]. Interestingly, ARS2 is also used in RNA production and RNA decay. CBC binds to ARS2, which helps ARS2 bind to other RNA enzymes and the RNA itself. ARS2 is a scaffold protein in that it brings multiple functional proteins together with RNA to achieve an effect. It also helps in proliferation and mammalian development due to this RNA metabolism. ARS2 can conjoin with multiple proteins and has a multifunctional purpose [3].

Structural highlights

The PDB files for ARS2 are given below. As can be seen, ARS2 binds to CBC in the PDB structure 5006. It binds between the two subunits of CBC. The binding site is unknown, but as it is positioned between two subunits (an alpha helix in subunit 1, a beta sheet in subunit 2) in a pocket. The subunit residues of CBC are Lysine, Serine and Asparagine, or all polar compounds. With this being the case, the residues for the section of ARG2 in between the two subunits are most likely polar, as electrostatic interactions are favored between polar bonds. An image of CBC and ARG2 is below.

Figure 1. The interaction between CBC (Subunit 1 is green, subunit 2 is orange). and ARG2 (Grey) [1].

ARG2 also has been shown to bind to RNA. The exact residues for RNA binding are not known, but one source has determined that the N-terminus of the protein is the binding site of RNA. The RNA binds to the N-terminus of ARG2, while the rest of thew protein binds to CBC to hold RNA in place for maintenance or decay [4]. A crystal image of ARG2 has been solved in PDB. The N-terminus of the protein is highlighted below. It is to be noted that the ARG2 protein has many alpha helices, which may facilitate binding of RNA.

Image 2. The structure of ARG2. N-terminus is in upper right (orange) [2].

3D structures of arsenite resistance protein

Updated on 16-January-2022

6f7p, 6f7s – hARS2 residues 147-270+408-763 – human
6f7j, 6f8d – hARS2 residues 171-270+408-763

References

1.Bank, R. P. D. (2017a, August 6). RCSB PDB - 5OO6: Complex of human nuclear cap-binding complex with ARS2 C-terminal peptide. Www.rcsb.org. https://www.rcsb.org/structure/5OO6

2. Bank, R. P. D. (2017b, December 10). RCSB PDB - 6F7J: Crystal structure of Human ARS2 residues 171-270 + 408-763. Www.rcsb.org. https://www.rcsb.org/structure/6F7J

3.Melko, M., Winczura, K., Rouvière, J. O., Oborská-Oplová, M., Andersen, P., & Heick Jensen, T. (2020). Mapping domains of ARS2 critical for its RNA decay capacity. Nucleic Acids Research, 48(12), 6943–6953. https://doi.org/10.1093/nar/gkaa445

4.Schulze, W. M., Stein, F., Rettel, M., Nanao, M., & Cusack, S. (2018). Structural analysis of human ARS2 as a platform for co-transcriptional RNA sorting. Nature Communications, 9(1), 1701. https://doi.org/10.1038/s41467-018-04142-7

5.SRRT - Serrate RNA effector molecule homolog - Homo sapiens (Human) - SRRT gene & protein. (n.d.). Www.uniprot.org. Retrieved October 14, 2021, from https://www.uniprot.org/uniprot/Q9BXP5#interaction