Protein targeting

Protein targeting describes the mechanisms of a biological cell to transport proteins? to the appropriate organelle, to be inserted into a membrane, or to be secreted? to the outside. (This article deals with protein targeting of eukaryotes until noted otherwise.)

Protein translocation

In 1970, [Günter Blobel]? conducted experiments about the translocation of proteins across membranes. He was awarded the 1999 Nobel prize for his findings. He discovered that many proteins have a [signal sequence]?, a short amino acid sequence at one end, that functions like a [postal code]? for their target organelle. The translation of mRNA into protein by a ribosome takes place within the cytosol. If the synthesized proteins are intended to go to a different organelle, they can do this in two ways, depending on the protein.

Cotranslational translocation

The (N-terminal) signal sequence of the protein is recognized by a [signal recognition particle]? (SRP) while the protein is still synthesized by the ribosome. The ribosome then pauses, while it is transferred to a [SRP receptor]? on the membrane of the endoplasmic reticulum (ER). There, it is switched over to a protein channel into the ER. The nascending polypeptide chain (the protein) is inserted into the ER through the channel. In the ER, the protein is first covered by a [chaperone protein]? to cover it from the high amount of other proteins in the ER, giving it time to fold? correctly. Once folded, the protein is modified as needed (for example, by glycosylation?), and transported into the golgi apparatus for further processing and sorting. From there, it goes to its target organelle. On translocation into that organelle, the signal sequence will be cut off.

Posttranslational translocation

Even though most proteins are cotranslationally translocated, some are translated in the cytosol and later transported to their destination. That is the case for proteins that go to a mitochindrium?, a chloroplast, or a peroxisome; proteins that go to the latter have their signal sequence at the C Terminus. Also, proteins targeted for the nucleus are translocated posttranslational. They pass through the nuclear envelope via nuclear pores.

Transmembrane proteins

[Transmembrane protein]?s, often transmembrane receptors, pass through a membrane one or several times. They are inserted into the membrane by translocation, which is interrupted by a stop-transfer sequence, also called membrane anchor sequence.

Receptor-mediated endocytosis

Several molecules that attach to special receptors called [coated pits]? on the outside of cells cause the cell to perform endocytosis, an invagination of the plasma membrane to incorporate the molecule and associated structures. This mechanism is used for three main purposes:

1. The uptake of essential metabolites, for example, LDL?.
2. The uptake of some hormones and [growth factors]?, for example, [epidermal growth factor]? and [nerve growth factor]?.
3. The uptake of proteins that are to be destroyed, for example, antigens in phagocytotic? cells like macrophages?.

The receptor-mediated endocytosis can also be abused:

• Some viruses, for example, the [Semliki forest virus]?, get access to the cell through this mechanism.
• The poisons/toxins? of cholera? and diphteria? gain entry to the cell this way.

Protein destruction

Just like in factories, some proteins are created defective; others are damaged while in use, for example, by oxidative stress. To recycle these damaged proteins, proteins have very different [half lifes]?, mainly depending on their N-terminal amino acid residue. The recycling mechanism itself is mediated by ubiquitin (see there).

Protein targeting in bacteria

Also bacteria do not have organelles they can send proteins to, there are proteins to be incorporated into the plasma membrane, or to be secreted into the environment. The basic mechanism is similar to the eukaryotic one, and its principles have been conserved.

See also : biochemistry -- SNAP? -- SNARE?