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Proteasomes are compartmentalised proteases with sequestered active sites. They form large complex protein complexes within Eukaryotes as well as in some bacteria. They are found in the cell cytoplasm and within the nucleus. They function to regulate and control the concentration of specific proteins via ubiquitin targeted degradation deliberately destroying proteins via proteolysis.
Lysosomes on the other hand are membrane enclosed compartments filled with soluble hydrolytic enzymes that control intracellular digestion of macromolecules. They contain roughly 40 different types of hydrolytic enzymes from proteases to lipases known as acid hydrolyses. They are activated via proteolytic cleavage within an acid environment. This acid environment is maintained at 4.5-5.0 pH by the lysosome via a V-type ATPase in the membrane pumping H+ into the membrane.
Although the key function behind both organelles is the same, degradation their protein composition is dramatically different in order to provide specific function.
Structurally both organelles are very different. Proteases are structurally homogenous due to fact that they carry out a specific uniform function. This specificity is reflected within its structure, as the structure in high in complexity compared to that of the lysosome.
Lysosomes are structurally a lot simpler; however they form heterogeneous structures and vary dramatically in morphology. This reflects their wide and diverse variety of digestive functions that acid hydrolases mediate and the way lysosomes form.
Although the underlying functions of both organelles to degrade cell constituents are the same, the ways in which they function and their specificity is dramatically different which relates to their structure.
Structurally the proteasome is more complex but uniform/homogenous. Proteasomes are made up of a barrel-like complex consisting of a central hollow cylinder formed from multiple protein subunits. These are specific and highly important in allowing the proteasome to carry out its function.
As you can see from the diagram above the proteasome is formed from a 20S core particle (yellow) and two regulatory 19S caps on either end (blue). The core 20S particle is hollow and provides an enclosed cavity in which proteins are degraded. It forms a stack of four heptameric rings. The outer two rings are made up of seven alpha subunits serving as docking domains forming a 'gate' blocking unregulated access. The inner rings contain seven beta subunits containing six protease active sites for protein degradation. This is where the target proteins are threaded into the proteasome core where they are subsequently degraded.
The two 19S caps are each formed of 19 individual proteins. 10 of which form a base binding directly to the 20S core and 9 forming a polyubiquitin bound lid. It is the 19S cap which is responsible for stimulating the proteolytic activity of the 20S core.
The 19S caps act as regulated 'gates' at the entrances of the proteolytic chamber and are responsible for binding a targeted protein substrate to the proteasome. It is able to recognise the substrate as it is marked for destruction by a covalent attachment of a recognition tag formed from a small protein called ubiquitin. The proteins within the within the ring structure of the 19S cap belong to a large class of protein 'unfoldases' known as AAA proteins. These are hexameric structures formed from six subunits each belonging to the AAA family of proteins. The ATP-dependent activity of which, functions to facilitate the entry of the ubiquitin tagged substrate molecule. The structure of the hexameric protein unfoldase is shown below.
The ATP-bound form of the hexameric ring of AAA proteins binds to the targeted substrate protein that has been ubiquitin marked for unfolding. A conformation change made irreversible by ATP hydrolysis pulls the substrate into the central core via unfolding, where it quickly moves through the pore via successive rounds of ATP-hydrolysis, acting to degrade the protein within the proteolytic core (protease active sites). The gate is opened the ATPases C-termini, which bind into specific pockets in the top of the 20S acting to 'open the gate'.
The complexity of its structure is therefore subject the specific nature of its function and the processivity of its mechanism.
The structure of lysosomes is dramatically different to that of a proteasome. The inherent protein structures of lysosomes are simple in comparison. They are made up of a simple phospholipid bilayer forming the outer plasma membrane with intermittent glycolated membrane transport proteins. Although the structural composition is relatively simple in contrast to that of a proteasome, the interior protein constituents are particularly diverse and heterogeneous in morphology. This is made up of a hydrolytic enzyme mixture which is specific to that particular lysosomes function. Where the function of the proteasome is uniform and specific, the functions of lysosomes are subject to the hydrolytic mixture of enzymes within the interior. The structure of a lysosome is shown below:
Although the protein composition is simpler, it is also unique to its function. The plasma membrane is made up of highly glycosylated proteins which help to protect them and the surround cell from destruction by lysosomal proteases in the lumen. Similarly to the proteasome, the lysosome has a specific ATPase function. It contains a V-type ATPase within the membrane which is critically important in maintaining the lumens acidic pH. The acid hydrolases are activated by proteolytic cleavage within an acidic environment of a pH between 4.5-5.0; this is maintained by the V-type ATPase. It acts to pump H+ into the lumen of the organelle via ATP hydrolysis. This energy through the proton gradient formed also helps to drive the transport of small metabolites.
The heterogeneous morphology of the lumen interior in terms of enzyme (protein) complexity reflects the wide diversity of digestive functions that acid hydrolases mediate through the structure of the lysosome: the breakdown of intra- and extracellular debris, the destruction of phagocytosed micro-organisms and the production of nutrients for the cell. Instead of structural complexity leading to specific function such as that in proteasomes. Lysosomes are morphological complexity rather than structural complexity, which allows for much greater diversity in function, defined by common function of degrading intracellular material. Their formation and subsequent activity is discussed below.
Newly synthesised lysosomal proteins are transferred into the lumen of the ER, transported through the Golgi apparatus, and then carried from the Trans golgi network to late endosomes by means of clathrin-coated transport vesicles. The lysosomal hydrolases contain N-linked oligosaccharides which are modified via mannose phosphorylation; this is through mannose 6-phosphate (M6P) group recognition by M6P receptor proteins that secretes the hydrolases and packages them into transport vesicles to deliver to endosomes. The low pH causes dissociation from M6P receptors making the hydrolase transport unidirectional. Clathrin-coated vesicles used to transport and deliver resident lysosomal membrane proteins.