Protein targeting

Protein Targeting refers to the biological mechanism through which protein transportation takes place. In simpler terms, protein sorting or targeting is a mechanism set through which cells help to transport protein within the membranes to appropriate destinations. The protein targeting can occur within or outer cell membrane. 

The delivery process of protein is directed through the information contained within. Therefore, cells need to sort out proteins correctly through the cells; else, the body is exposed to varied types of disease. 

Mechanism of protein targeting

Proteins are sorted as endoplasmic reticulum, mitochondria, chloroplasts, peroxisomes through various mechanisms performed by cells. The process for protein sorting can occur during protein synthesis or after the synthesis has been performed through ribosome translation.  

The majority of the integral membrane proteins, secretory and lysosomal, are usually done through ER lumen. The ER modifies protein for sorting the same. The proteins with membrane targeting lead insertion of protein into lipids bilayer. 

The water-soluble proteins are targeting results in protein translocation through the membrane within the organelle interior. After the synthesisation of protein for cytosol, they do not change their destinations. 

Proteins like mitochondria and chloroplast are synthesised and then released from ribosomes. These proteins are further bound through cytosolic chaperone proteins. After which, they are delivered to targeted organelle receptors.

Proteins with nuclear-like DNA and RNA histones, topoisomerases and polymerases regulate gene expression containing NLS (Nuclear localisation signal). The NLS remains even when the translocation of protein takes place. On the contrary, NLS could be easily located at any destination following the primary sequence, while ER localisation usually follows signal sequencing. 

Most NLS contains residuals of amino acids (approximately 4-8) combined with consecutive bases. 

Protein Sequencing 

Protein targeting is explained through sequencing. First, they are sorted as ER, which contains a terminal signal sequence of amino acids that helps to translocate protein ER lumen. G Blobel first proposed signal sequence functions in 1970. 

 The signal sequence contains 13- 36 residues of amino acids, of which 10-15 are hydrophobic aminos. George Palade demonstrated that ER protein signal sequence synthesises with ribosomes attached to rough ER. Hence, the signal sequencing directs ribosomes towards ER. 

 In the targeting sequence, protein is not the ultimate destination. Hence, part of it is a polypeptide. These are cleaved through signal peptidase, which might remain a permanent protein part. Also, they might be easily located onto N-, or at the midst of any protein element. 

Drug Protein Targeting 

Target protein examples for drug action can be cited as receptors, enzymes, carrier molecules, ion channels. The above examples are chosen for the drug as they are effective because it helps to bind together targeted proteins. 

Protein is usually targeted for drugs as, during the disease recovery process, it helps to generate therapeutic impact. Drug targeting includes G- coupled proteins (50% of the drugs are targeted at this type), enzymes like protease, kinases, ion channels like ligand-gated, voltage-gated, and nuclear receptors. 

 The target usually starts with identifying protein functions for healing the disease. This target identification is then followed by molecular mechanisms encountering the cells. 

Synthesisation of proteins

 Proteins start to synthesise onto cytosolic ribosomes. Protein targeting or translocation occurs through Co- translational and post-translational. If protein is done for cytosolic functions, the synthesis shall be completed through free ribosomes. After which, the peptide is then released into the cytosol. 

The daily protein target is approximately 20-25 grams of proteins within 1.5 to 2 hours. This largely depends on protein weight. For example, lighter weight proteins can be easily digested. Hence, the body synthesises approximately 10 grams every hour. 

Protein is required for body functioning, body mechanism targets and transports to the required cells for proper functioning. Therefore, any adult must consume a minimum of 0.8 g protein aligned with per kg of total body weight. 

In co-translational protein targeting, the protein is secreted from the cell membrane. For this ribosome, membranes are destined with nascent peptides towards ER. Thus, protein sorting is done during the translation processes. 

During the co-translational translocation protein, N terminal signal sequencing is generally depicted as a signal recognition particle during the ongoing protein synthesisation onto the ribosome. 

After the synthesis is paused, the complex ribosome protein is transported towards SRP receptors. Even if most proteins are transported through co-translational, some residues will be converted in the cytosol and transported later. 

Post-translational protein targeting includes the synthesis of proteins destined for the nucleus, mitochondria and peroxisomes. The synthesis is finished onto cytoplasmic ribosomes, after which peptide is released into the cytosol to sort out the proteins in a post-translational form. 

Conclusion 

Protein targeting is a biological mechanism for the synthesis and transportation of proteins. The protein content guides its synthesis and transportation within the body. After the protein is produced from the ribosome, they are translocated onto ER.

 Protein is synthesised and transported through two processes. One is co-translational, transportation continuous during ongoing protein synthesis. The synthesis is paused as complex proteins are transported to the SRP receptor.  

The other process is post-translational, in which few proteins are translated into cytosol. Instead, this is transported to the destination later on.