Protein sorting

INTRODUCTION :

Protein sorting is also known as protein targeting. Protein sorting or protein targeting. Is the biological mechanism by which proteins are transported to their appropriate destination within or outside the cell.

• Protein can be targeted to-
• The inner space of an organelle
• Different intercellular membrane
• The plasma membrane
• The exterior of the cell via secreation.

Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell, any error or dysfunctions in sorting may lead to several disease.

Protein sorting generally means transportation of protein. The process starts after the formation of protein by the process of translation (through which information encoded in Messenger RNA(M RNA ) directs the addition of amino acids)

PROTIEN SORTING :

The process by which proteins are targeted to a specific organelle is called protein sorting.

• It can be of two types –
• Signal based sorting– Specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation.
• Vehicle based trafficking – it includes the movement of protein in membrane bound structures called transport vehicles.

TARGETING SIGNALS :

Signal peptides act as targeting signals . It allows the cellular transport system to route proteins to particular intracellular or extracellular region.

The signal peptide is typically cut by a signal peptidase Once a protein reaches its destination.

As a result , signal peptides are absent from the majority of mature proteins.

The signal peptides are called targeting peptides. They are of two types-

1.  Presequences
2. Internal targeting peptides  

PROTEIN TRANSLOCATION :

Protein translocation is the process by which proteins move between cellular compartments . Proteins intended for secretion or a particular organelle must be transported because the cytosol is where the ribosome translate mRNA into protein.

1. Co- translation translocation
2. Post- translation translocation

Co- translation translocation is the term for the process, which can also take place during translation. It occurs. When membrane bound ribosomes insert growing nascent polypeptide chains directly into an ER translocation pore.

Post translation translocation occurs after translation is finished. It is the process where a sizable fraction of proteins designed for ER are first synthesized in the cell cytosol and then transported across the ER membrane.

The translation of mRNA into protein by ribosome takes place within the cytosol . If the synthesized proteins belong in the different organelle they can be transported there in either of two ways depending on the protein.

1. Co translational translocation – As the name indicates, here translocation of protein occurs in translation. The N- terminal signal sequence for the protein is recognised by a signal recognition particle (SRP) While the protein is still being synthesized on the ribosome.

The synthesis of protein pauses while the ribosome protein complex is transferred through an SRP receptor on the ER , a membrane enclosed organelle. There , the nascent protein is inserted into the Sec 61 translocation complex (translocon) that passes through the ER membrane.

The signal sequence is immediately cleaved from the polypeptide once it has been translocated into the ER by signal peptidase in secretary proteins.

This signal protein sequence processing differs for some ER transmembrane proteins within the ER, the protein is first covered by a chaperone protien to protect it from the high concentration of other protein in the ER , giving it time to fold correctly .

Once folded , the protein is modified as needed then transported to the Golgi apparatus for further processing and goes to it’s target organelles or is retained in the ER by various ER retention mechanism.

• Post translocational translocation – As the name indicates, the translocation of proteins occur after the completion of translocation . Even though most proteins are co translationally translocated , some are translated in the cytosol and later transported to their destination.

This occurs for proteins that go to a mitochondrion , a chloroplast, or a peroxisome .

Also , proteins targeted for the nucleus are also translocated post translationally they pass through the nuclear envelope via nuclear pore.

This also occurs for proteins that go to a ER lumen .

• ER Lumen :

– After protein is released into the cytoplasm it will go to the ER lumen and several other targetting organelles.

– Here chaperon is attached to protein to prevent folding .

– Sec 61 translocation complex (translocon) is present in the membrane of ER.

The N- terminal signal sequence bind with the translocon or interact with the translocon which cause the opening of translocon .

– The signal sequence is immediately cleaved from the polypeptide once it has been translocated into ER lumen by signal peptidase.

– Bip Protein hydrolyse the ATP and bind with the protein causes generation of energy which helps the molecule to pull the protein inside the lumen.

– Sec 63 complex helps Bip protein for ATP hydrolysis

– The protein finally enters lumen and folds.

– Bip also prevents the protien from folding.

– After folding of protiens recycling of Bip ATP takes place.

– Bip is a type of Hsp( heat shock protein).

• MITOCHONDRION :

– The majority of mitochondrial proteins ade created as cytosolic precursors with uptake peptide signals, while certain proteins in the organelle are made from mitochondrial DNA.

– Depending on their sequences, unfolded proteins bounded by the cytosolic chaperone Hsp 70 and sent to the mitochondria may be localised to 4 different portions. They could be directed at the inner membrane, intermembrane gap, outer membrane or mitochondrial Matrix.

– Health and disease have been related to flaws in one of the mechanisms.

• CHLOROPLAST :

– Depending on the sequence, proteins may be sent to the stroma, thylakoid lumen, other envelope, inner envelope, or thylakoid membrane of chloroplast.

– Because they typically lack a cleavable sorting sequence, proteins that are directed to the chloroplast envelope are laterally displaced by membrane sorting complexes.

– The TOC and TIC comlexes inside the chloroplast envelope are required for the general import of the bulk of proteins from the cytosol.

– The translocase of the outer chloroplast envelope is referred to as TOC, and of the inner chloroplast envelope is referred as TIC.

– In the stroma the stromal import sequence is cleaved off and intra chloroplast sorting and folding continues.

• PEROXISOMES :

– All peroxisomal proteins are encoded by nuclear genes.

– There are 2 types of peroxisomal targetting signal –

   1. C – terminal tripeptide with the consensus sequence (S/A/C) – (K/R/H) – (L/A).

        The most common PTS1 is SLL(serine – lysine – leucine).

         Most of the peroxisomal matrix posses PTS1.

   2. Few proteins posses PTS2, N – terminal non-peptide with a consensus sequence (R/K) – (L/V/I) – X5 – (H/Q) – (L/Q/K).

 – There are also proteins that posses neither od these signals. There transport is based on so called “piggy – back” mechanism ; such proteins associated with PTS1- possessing matrix proteins and are translocated into the peroxisomal matrix together with them.

CONCLUSION :

The process by which proteins are targeted to a specific organelle is called protein sorting or protein targeting. The translation of mRNA into the protein by a ribosome takes place within the cytosol. If the synthesised proteins ‘belong’ in the different organelles, they can be transported there in either of 2 ways, depend on the protein :

1. Co- translational translocation

2. Post- translational translocation

Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; error or dysfunctions in sorting have been linked to multiple disease.