What is Molecular Chaperon or Ubiquitious Protein?

Table of contents 

• Chaperon and Ubiquitination's Role in Protein Conformation or Function
• What is Molecular Chaperone? 
• What is Protein folding?
• The Role of molecular Chaperones and Ubiquitination in Protein Conformation
• Heat shock protein (Hsp70)
• Heat shock protein (Hsp60)

Chaperon and Ubiquitination's Role in Protein Conformation or Function 

What is Molecular Chaperone?

Molecular chaperones are the class of proteins that assist in stabilising non-native protein (the biologically relevant components of a cell but are misfolded proteins) conformations and promote folding into the native state whenever possible. Alternatively, misfolded proteins are eliminated by a cell via a degradation mechanism called the ubiquitin–proteasome system.

What is Protein folding?

Protein synthesis is carried out by ribosomes. In the beginning, ribosomes synthesise a linear chain of amino acids called the polypeptide chain. The stretch of mRNA specifies the amino acid sequence, and each amino acid in this polypeptide chain has its own unique property. For example, glycine is very hydrophobic, while arginine is very hydrophilic. These properties of amino acids depict the three-dimensional structure of the protein. The outside of the protein possesses the hydrophilic amino acids, while the inside of the protein must conserve the hydrophobic amino acids. The secondary structure of proteins (alpha helices and beta sheets) is acquired by hydrogen bonds between the polypeptide chains. After the primary and secondary structures, the helices constitute the tertiary structure. Protein folding must be precise in its three-dimensional form and must not be aggregated or degraded. The unfolded and misfolded proteins result in non-native protein aggregation, which is an inactive form but, in some cases, may lead to diseases. 

The Role of Molecular Chaperones and Ubiquitination in Protein Conformation 

In molecular biology, the chaperones are defined as "the molecular chaperones are the proteins that have the ability to assist and stabilise the conformation of non-native folding. The ubiquitous proteins, which are an amazingly diverse family of proteins, are also among the most abundant intracellular proteins. The basic function of chaperones is posttranslational modification of proteins, so ubiquitous proteins mediate correct protein folding, inhibit misfolding, and prevent other proteins from degradation and non-native aggregation during their tertiary structure formation. Chaperones sometimes interact with other packaging called ancillary proteins. Both proteins together regulate the folding of other proteins. Chaperones are ubiquitously expressed and are found in all cellular compartments of the eukaryotic cell (except for peroxisomes). In general, the concentration of chaperone increases in response to diverse stresses in order to prevent the proteins' folding and for the stabilisation of the protein. An example of chaperon proteins are the "heat shock proteins" (Hsps), which are discovered in bacteria under stress conditions. The bacteria produce a number of such proteins under stressful conditions, such as higher temperatures, pH variation, and hypoxic conditions. 

Fig 2: Role of Chaperon in quality control of protein.

Two examples of Hsps are Hsp70 and Hsp60. 

Heat shock protein (Hsp70)

The Hsp70 chaperone proteins are folding catalysts that help in the refolding or misfolding of aggregated proteins and in the folding and assembling of new proteins. The Hsps 70 contains two different domains, namely the N terminal and the C terminal. The N terminal contains the ATPase site while the C terminal domain binds to the substrate. The N terminal ATPase hydrolysis site helps the C terminal to open and bind to the substrate. 

Hsp70 recognises the "extended region" of an unfolded polypeptide chain. This extended region contains many hydrophobic residues. HSP70-binding prevents the aggregation of these proteins. 

Fig 3: Domain organization and 3D structure of Hsp70

Heat shock protein (Hsp60)

Hsp60 chaperone proteins bind to exposed hydrophobic residues of unfolded proteins and help to form aggregates that are stable but inactive. Hsp60 proteins could not prevent a protein's aggregation, but rather they functioned to isolate and quarantine an unfolded protein. This isolation prevents a polypeptide chain from aggregating into clumps with other chains within the cytoplasm.

Hsp 60 contains 14 different protein components. These proteins are made of 7 proteins which are placed on top of each other and form two rings. Unfolded proteins can then fold safely within these rings because the Hsp60 protein does not interfere with the unfolded protein (newly formed proteins) or aggregate with other unfolded proteins. Hsp60 also has two different domains: the protein binding motif, where ATP binds, and the unfolded proteins can enter the hole between the two rings. The enclosed state, called the folding-active state, is then activated by ATP hydrolysis. This conformational change prevents the unfolded protein from leaving the ring and assists the protein folding. The state lasts for around 15 seconds and the folded protein  after proper folding, is released into the cytoplasm. The enclosed state then deactivates and the protein changes back to its conformation.

Fig 4: Domain organization and 3D structure of Hsp60.