PROTEIN HOMEOSTASIS IN ASGARD ARCHAEA
1.0 Protein Homeostasis by UPS (Ubiquitin proteasome system)
Protein Homeostasis, also regarded as the proteostasis, denotes the subtle intracellular balance amid a generation of the newly synthesized proteins and the quick disposal of misfolded and damaged proteins, which are beyond refolding or repair (Ciechanover & Kwon, 2015). Protein homeostasis is crucial for the living cell since it assists an organism in upholding the normal cellular functions of the cellular functions. Dysregulation of the cellular protein homeostasis can trigger illness. Thus, living organisms, particularly Asgard archaea cells, have initiated various sophisticated mechanisms necessary to degrade proteins, which are part of the entire process of protein quality control. One such mechanism is the UPS, in UPS protein substrate besieged for degradation is covalently improved by the polyubiquitin chains and directed to the proteasome for proteolysis (Kern & Behl, 2019).
Moreover, apart from disposing of misfolded and damaged intracellular proteins, UPS plays a crucial role in numerous cellular pathways, such as signaling pathways, and cell cycle progression where spatially and temporarily controlled fashion is essential safeguarding normal cellular functions (Ohtaki, Noguchi & Yohda, 2010). UPS comprises a series of finely orchestrated enzyme activities that ultimately result in the protein degradation and polyubiquitination by 26S proteasome found in eukaryotic cells. The E1-E2-E3 enzymatic cascade arbitrates protein ubiquitination. Firstly, ubiquitin, which contains a highly preserved 76 amino acid protein, is triggered by the E1 enzyme in the existence of ATP to create an E1-ubiquitin covalent intermediate. Consequently, the conserved cysteine residue in the E1 creates a thioester with a C-Terminal glycine. Secondly, E1-ubiquitin thioester moves beyond ubiquitin into the cysteine residue in the E2, also known as ubiquitin-conjugating enzyme through a transthiolation reaction (Miranda et al., 2011). Lastly, E3 ubiquitin ligase catalyzes ubiquitin transmission from the E2-ubiquitin thioester into a particular lysine residue on a protein substrate.
Fig 1.0. Ubiquitin-Proteasome System. It contains E1, E2, E3 enzymatic cascades necessary to facilitate protein ubiquitination of the cellular components such as the protein aggregates, proteins, and a large number of the cellular compartments and organelles (Nandi, Tahiliani, Kumar & Chandu, 2006).
2.0 Protein Homeostasis by Lysosomal Degradation
On the other hand, lysosomal degradation denotes the highly preserved eukaryotic pathway meant to enhance lysosomal degradation. This is the major pathway used for the protein homeostasis in the eukaryotic cells; it involves the uptake of the proteins by lysosomes. Lysosomes contain a collection of digestive enzymes, which involves numerous proteases (Maupin-Furlow, 2000). They conduct various functions, including the digestion of the extracellular protein’s uptake by endocytosis and a gradual turnover of cytosolic proteins. For the protein to be successfully degraded by lysosomes without degrading the cell’s contents, cellular proteins are first absorbed by lysosomes (Ebrahimi, Wahlster & McLean, 2012). Autophagy establishes vesicles (autophagosomes) where cytoplasmic organelles or cytoplasm are enclosed in a membrane formed from the endoplasmic reticulum. The established vesicles combine with the lysosomes; hence degradative lysosomal enzymes conduct the digestion of their contents. Uptake of the proteins in the autophagosomes is non-selective, resulting in a slow degradation of the cytoplasmic proteins. However, some of the protein absorbed by the lysosomes are non-selective, for instance, lysosome can take up degrade particular lysosome in a selective manner due to the cellular starvation (Maupin, 2013). This protein contains the amino acid sequences alike to the extensive consensus sequence Lys-Phe-Glu-Arg-Gln. The forms of proteins exposed to degradation by lysosomal degradation are thought to be long-lives and dispensable.
Fig 2.0 Lysosomal Degradation Pathway. The pathway constitutes a multivesicular endosome, the lysosome. The entire process moves from autophagosome, amphisome to autolysosome. The degradation of proteins occurs in the autolysosome.
The two critical cellular degradation pathways to facilitate the protein homeostasis (Autographic-lysosomal pathway and proteasomal degradation). The protein folding is regulated by chaperones to facilitate an accurate three-dimensional structure of the protein. The misfolded proteins are transformed into two critical principal degradation pathways (Huber & Teis, 2016). Mostly, Ubiquitin proteasome represents the degradation of the dysfunctional proteins, such as protein turnover. Autophagosomal pathways clear aggregates (for instance, disease-proteins), protein oligomers, the entire organelles, and intruders (viral and bacterial infections).
3.0 Protein Homeostasis in Eukaryotes
The Asgard, as the archaea family, is considered to be the adjoining member of the eukaryotic organisms that have been discovered until to date (Fournier & Poole, 2018). Asgard tends to express membrane-associated intricacies indicative of the vesicular trafficking structures consistent with the evolutionary progress of the protein degradation systems. As discovered from the lysosomal degradation system, similar to eukaryotes, the archaeal species tend to possess’ unequivocal homologues of a ubiquitin-proteasome degradation apparatus. Hence, both archaeal and eukaryotes tend to share similar characteristics (Akil et al., 2019). The protein homeostasis in Asgard archaeal plays a significant role in creating a good understanding of eukaryotes. This can easily be related since archaea tend to share similar characteristics with the eukaryotes, particularly the DNA and the protein homeostasis processes. Both Asgard and eukaryotes conduct their homeostasis using similar molecular apparatus (Spang et al., 2018). Hence having a good understanding of the protein homeostasis by UPS and Lysosomal degradation in Asgard archaea suggests that a similar process of protein homeostasis
might characterize the eukaryotes.
Eukaryotes rely primarily on the proteasome system for the protein homeostasis; the proteasome is a huge protein that archetypally recognizes and then degrades ubiquitinated substrates (Dacks, Peden & Field, 2009). Since Archaea and Eukarya emanate from similar “super-domain” understanding of the various components of the Archaea cell and how they work to achieve protein homeostasis, they can play a critical role in understanding the way eukaryotic cells work to achieve protein homeostasis (Zaremba, 2017). Hence the Asgard archaea have led to increased eukaryotic-archaeal relationships, particularly in the phylogenetic analyses (Fu et al., 2016). Asgard encrypts genes involved in various eukaryotic features systems, most of which were prior regarded as eukaryotic-specific.
Figure 3.0 Protein Homeostasis in Eukaryotes. The image indicates the protein homeostasis in Eukaryotes. It resembles primary cells used by Asgard archaea in protein homeostases such as the proteasome, chaperones, the degradation, and autophagosome (Zaremba, 2017).
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