Last updated on January 11, 2020 at 13:46
- Proteins are synthesized in the cytosol (or the mitochondria), but many need to be transported into other organelles in the cell, like the nucleus, or Golgi. This is done with the help of signal sequences, small polypeptide sequences on the end of a polypeptide that direct the polypeptide to the correct organelle.
- The signal sequence is often removed when the protein reaches its target
- The signal sequence is most often found on the N-terminus, only sometimes on the C-terminus.
- Examples of signal sequences are PTS1 on the C-terminal end, and PTS2 on the N-terminal end
Proteins are synthesized in the cytosol, on ribosomes. However, proteins are needed in other cellular compartments as well, like the nucleus, or ER. Proteins must therefore be transported from cytosol into these targets. This is done by the help of signal sequences, a short sequence of nucleotides on the N-terminus (more common) or C-terminus (less common) of a protein. These sequences are recognized on the membrane of the target organelle, and the polypeptide is transported inside. On the inside, the signal sequence may be cleaved off, but not in all cases, as we shall see.
Because signal sequences are most commonly found on the N-terminus, and because the ribosome synthesize the N-terminus of proteins first, the signal sequences are often the first part of the protein to be translated. When a protein is targeted for transport into the ER, a protein called SRP binds to the N-terminus signal sequence, while the protein is still being synthesized. SRP consumes GTP in this process. SRP then “carries” the ribosome, which has now paused the translation, to the ER. When at the ER, the ribosome continues the translation, now “feeding” the translated polypeptide chain directly into the ER. Inside the ER, the signal sequence is removed by a signal peptidase. When translation is finished, the product is now inside ER, and the ribosome dissociates.
Inside the ER, proteins can be further modified, like with disulphide bond formation, or glycosylation. Tunicamycin is an antibiotic that inhibits this glycosylation. Following this, the proteins travel from ER to Golgi in transport vesicles. In Golgi, glycosylated proteins may be further modified. After this, Golgi sorts the proteins, and sends them to their final destinations.
Protein targetting to nucleus
The signal sequence that target a protein for the nucleus is not cleaved off when the protein has entered the nucleus. This is because during cell division, the nuclear envelope is broken down, so all proteins inside are dispersed through the cytoplasm. After cell division, the nuclear envelope is rebuilt, and the proteins must find their way back in. This signal sequence is called the nuclear localization sequence, or NLS. NLS is different from other signal sequences in that it may be found anywhere on the protein, not just on the ends.
Importin is a protein which is involved in the nuclear targetting of proteins.
Protein targetting to mitochondria
Unlike proteins targeted for transport into ER, proteins targeted for the mitochondria are synthesized completely in the cytosol before being transported. They are then transported to receptors on the surface of the mitochondria, from where they are transported into the mitochondria, where the signal sequence is removed. Proteins involved are Tom20, Tom40, Tim23 and Tim44.
Protein targetting to peroxisomes
Proteins targeted for transport into peroxisomes contain the signal sequence PTS1 on the C-terminus, or PTS2 on the N-terminus.
Protein targetting of transmembrane proteins
Transmembrane proteins, proteins that are embedded in a membrane, reach their target membrane by containing special signal sequences called internal stop-transfer anchor sequences (STA) or internal signal-anchor sequences (SA). These proteins are transported through the membrane they should be embedded in, but when the SA or STA reaches the transporter, the protein is lodged in the membrane. Type IV transmembrane proteins contain many SA’s and STA’s, so this process is repeated, so many parts of the proteins are embedded in the membrane.
Cells depend on external proteins to a large degree. For cells to be able to take in for example LDL, transferrin, peptide hormones or circulatory proteins from outside, receptor-mediated endocytosis is needed. Receptor-mediated endocytosis is a process where an extracellular molecule, like LDLm binds to a receptor on the cell surface and is subsequently endocytosed.
There are many proteins involved, but the most important are clathrin and caveolin.
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