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 pit]?s 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:
- The uptake of essential metabolites, for example, LDL?.
- The uptake of some hormones and [growth factor]?s, for example, [epidermal growth factor]? and [nerve growth factor]?.
- The uptake of proteins that are to be destroyed, for example, antigens in phagocytotic? cells like macrophage?s.
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/toxin?s 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 life]
?s, 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?