Thursday, November 17, 2011

Protein Sorting

Protein Mobilization between compartments

Almost all proteins are synthesized on ribosomes in the cytosol but a few find their origin on the ribosomes in the mitochondria or chloroplasts.

These newly synthesized proteins carry out important functions in different organelles where they must be promptly delivered.

But how does the cell know which newly synthesized protein goes to what organelle?



Well, this is achieved with the help of "sorting signals" that facilitate delivery of proteins to their concerned organelles (more about sorting signals later in the post)

There are 3 fundamentally different ways by which newly synthesized proteins are sorted and delivered to carry out their functions in organelles:


  1. Gated transport - cytosol <==> nucleus via nuclear pore complexes
  2. Transmembrane transport - cytosol ==> ER, mitochondria, peroxisomes, plastids via protein translocators
  3. Vesicular transport - ER <==> Golgi, ER ==> endosomes, lysosomes etc. Transport vesicles ferry proteins from one compartment to another

Signal Sequences direct proteins to their correct address

There are 2 types of sorting signals:
  1. Signal Sequence - typically consists of 15-60 amino acids in a continuous stretch. It is (almost always) removed by signal peptidases once the sorting process is complete.
  2. Signal Patch - this is a three-dimensional arrangement of specific atoms recognized by sorting receptors when the protein folds up. This means that the atoms do not actually have to be in physical proximity to each other in the protein's unfolded form. Another thing that differentiated signal patches from signal sequences is that they often persist in the protein even after the sorting process is complete.

What do the signal sequences tell the cell?

Signal sequences specify the destination where the protein is to be delivered. For instance, a signal may specify that a protein needs to be imported into the ER while another may specify that the protein needs to be retained within the lumen of the ER. Yet another signal may specify that the protein needs to be imported either into mitochondria, nucleus, peroxisomes etc. This "specification" depends on the characteristics and types of amino acids present in the stretch.


Are signal sequences sufficient to direct a protein to its concerned organelle?

Well, it seems that signal sequences are not only sufficient but also necessary to direct a protein to an organelle.

Experiments were carried out where the signal sequences were either transferred or deleted altogether from a protein. The resulting protein ended up in a location where it normally would not be found.

This can be clarified with an example given in Alberts et al. Proteins destined to travel to the ER contain a signal sequence while those required to remain in the cystosol lack the sequence. When sequence from the ER protein is added to the cytosolic protein, the cytosolic protein ends up in the ER. Not surprisingly, when the signal sequence is removed from the ER protein, it remains in the cytosol instead of being delivered to its rightful destination!


Next Post: Nuclear Pore Complexes!

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