Protein targeting

Protein targeting includes the mechanisms by which a biological cell transports proteins to the appropriate organelle for insertion into a membrane or secreted[?] to the outside. (This article deals with protein targeting in eukaryotes except as noted.)

Table of contents 1 Protein translocation 1.1 Cotranslational translocation 1.2 Posttranslational translocation 1.3 Transmembrane proteins 2 Receptor-mediated endocytosis 3 Protein destruction 4 Protein targeting in bacteria

Protein translocation In 1970, Günter Blobel conducted experiments on 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[?], that is, a short amino acid sequence at one end that functions like a postal code for the target organelle. The translation of mRNA into protein by a ribosome takes place within the cytosol. If the synthesized proteins "belong" in a different organelle, they can be transported there in either of 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 being synthesized on the ribosome. The synthesis pauses while the ribosome-protein complex is transferred to an SRP receptor[?] on the endoplasmic reticulum (ER, which is a membrane-bound organelle). There, the nascent protein is inserted into a protein channel that passes through the ER membrane. Within the ER, the protein is first covered by a chaperone protein[?] to protect it from the high concentration of other proteins in the ER, giving it time to fold correctly. Once folded, the protein is modified as needed (for example, by glycosylation[?]), then transported into the Golgi apparatus for further processing and sorting. From there, it goes to its target organelle. Upon translocation into that organelle, the signal sequence is removed.

Posttranslational translocation

Even though most proteins are cotranslationally 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 (proteins that go to the latter have their signal sequence at the C terminus). Also, proteins targeted for the nucleus are translocated post-translation. They pass through the nuclear envelope via nuclear pores.

Transmembrane proteins

The amino acid chain of transmembrane proteins, which often are transmembrane receptors, passes through a membrane one or several times. They are inserted into the membrane by translocation, until the process is interrupted by a stop-transfer sequence, also called a 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:

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

Receptor-mediated endocytosis can also be "abused":

• Some viruses, for example, the Semliki forest virus[?], enter the cell through this mechanism.
• Cholera and diphtheria toxins also enter the cell this way.

Protein destruction Defective proteins are occasionally produced, or they may be damaged later, for example, by oxidative stress. Damaged proteins can be recycled. Proteins can have very different half lives, mainly depending on their N-terminal amino acid residue. The recycling mechanism is mediated by ubiquitin.

Protein targeting in bacteria Bacteria do not have organelles they can send proteins to, but some proteins are incorporated into the plasma membrane or secreted into the environment. The basic mechanism is similar to the eukaryotic one.