Protein targeting (2)

Sorting of proteins to both chloroplasts and mitochondria

Many proteins are needed in both mitochondria and chloroplasts. In general the targeting peptide is of intermediate character to the two specific ones. The targeting peptides of these proteins have a high content of basic and hydrophobic amino acids, a low content of negatively charged amino acids. They have a lower content of alanine and a higher content of leucine and phenylalanine. The dual targeted proteins have a more hydrophobic targeting peptide than both mitochondrial and chloroplastic ones.

Sorting of proteins to peroxisomes

All peroxisomal proteins are encoded by nuclear genes.

To date there are two types of known Peroxisome Targeting Signals (PTS):

Peroxisome targeting signal 1 (PTS1): a C-terminal tripeptide with a consensus sequence (S/A/C)-(K/R/H)-(L/A). The most common PTS1 is serine-lysine-leucine (SKL). Most peroxisomal matrix proteins possess a PTS1 type signal.

Peroxisome targeting signal 2 (PTS2): a nonapeptide located near the N-terminus with a consensus sequence (R/K)-(L/V/I)-XXXXX-(H/Q)-(L/A/F) (where X can be any amino acid).

There are also proteins that possess neither of these signals. Their transport may be based on a so-called "piggy-back" mechanism: such proteins associate with PTS1-possessing matrix proteins and are translocated into the peroxisomal matrix together with them.

Diseases

Peroxisomal protein tran

sport is defective in the following genetic diseases: Zellweger syndrome. Adrenoleukodystrophy (AL

D).

Refsum disease

Receptor-mediated endocytosis

Several molecules that attach to special receptors called clathrin 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 into endosomes. 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, diphtheria, anthrax, tetanus, botulinum, and

other bacterial toxins 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 lifes, mainly depending on their N-terminal amino acid residue. The recycling mechanism is mediated by ubiquitin.

Protein targeting in bacteria

With some exceptions, Bacteria lack membrane-bound organelles as found in eukaryotes, but they may assemble proteins onto various types of inclusions such as gas vesicles and storage granules. Bacteria may have a single plasma membrane (Gram-positive bacteria), or an inner membrane plus an outer membrane separated by the periplasm (Gram-negative bacteria). Proteins may be incorporated into the plasma membrane, or either trapped in the periplasm or secreted into the environment, according to whether or not there is an outer membrane. The basic mechanism at the plasma membrane is similar to the eukaryotic one. In addition, bacteria may target proteins into or across the outer membrane. Systems for secreting proteins across the bacterial outer membrane may be quite complex and play key roles in pathogenesis. These systems may be described as type I secretion, type II secretion, etc.

In most Gram-positive bacteria, certain proteins are targeted for export across the plasma membrane and subsequent covalent attachment to the bacterial cell wall. A specialized enzyme, sortase, cleaves the target protein at a characteristic recognition site near the protein C-terminus, such as an LPXTG motif (where X can be any amino acid), then transfers the protein onto the cell wall. An system analogous to sortase/LPXTG, termed exosortase/PEP-CTERM, is proposed to exist in a broad range of Gram-negative bacteria.

Secretory pathways

The secretory pathway includes vesicular traffic, secretion, and endocytosis. Secretory proteins follow this pathway.

Early stages

Retrograde transport is common in the early stages. Proteins that have been successfully delivered to the Golgi apparatus advance through cisternal progression.

Later stages

Coated vesicles mediate several transport steps.

References

1. Kanner EM, Friedlander M, Simon SM. (2003). "Co-translational targeting and translocation of the amino terminus of opsin across the endoplasmic membrane requires GTP but not ATP". J. Biol. Chem. 278 (10): 7920–7926.

doi:10.1074/jbc.M207462200. PMID 12486130. 2. Kanner EM, Klein IK. et al. (2002). "The amino terminus of opsin translocates "posttranslationally" as efficiently as cotranslationally". Biochemistry 41 (24): 7707–7715. doi:10.1021/bi0256882. PMID 12056902.

(From Wikipedia, the free encyclopedia)