Signal peptide

The signal sequence and signal peptide or transit peptide is a sequence of amino acids of a protein. This amino acid sequence decides the destination, the transport of the protein within the cell and secretion efficiency.

Occurrence and significance

Signal sequences are typically found in proteins whose destination is located, is located outside the cell in biomembranes or in compartments. As a signal sequence generally required for transport into the endoplasmic reticulum, chloroplasts, mitochondria, peroxisomes or the cell nucleus and their membranes. By combining different signal sequences, it is possible that proteins are imported simultaneously into different organelles, such as mitochondria and chloroplasts.

Although bacterial cells are not compartmentalized bacterial proteins may possess signal sequences. This can determine the proteins for transport to the cell membrane or the extracellular space.

Target compartments

Endoplasmic reticulum

A transport into the lumen or the membrane of the endoplasmic reticulum (ER) may be performed during protein biosynthesis ( cotranslational transport protein ), or only as a complete protein, which has been previously made ​​in the cytoplasm ( post-translational protein transport). Hydrophilic proteins with signal sequences are preferably transported post-translationally.

Proteins with hydrophobic signal sequences are cotranslationally transported against it. This is the " rough ER ", which is studded with ribosomes. The transport mechanism is complex and adjacent to the ribosome and are tied to the mRNA includes interacting proteins such as the signal recognition particle (SRP ) and ribosome -associated proteins. In addition, a SRP- receptor protein complex, and the tunnel ( SEC complex translocon ) is required in the membrane of the ER.

All secretory proteins and the majority of the membrane proteins incorporated in a signal sequence of a length of 15 to 50 amino acids at its N -terminus with certain properties. Even within a protein or the C-terminal signal sequences can be found.

The exact sequence of the individual amino acids is less important than their physical characteristics: a central hydrophobic core ( h) is flanked by polar amino acids N -terminal ( s) of positively charged amino acids and C -terminal ( c). The C-terminal region often contains helix -breaking amino acids such as proline or glycine. The N -terminal region is the least conserved. In most cases, the signal sequence is cleaved off after the passage of the actual membrane protein by the signal peptidase ( SPase ). The interface is defined by a small, non-charged amino acid residues at positions -3 and -1 of the C-terminal polar region of the signal sequence.

The amino acid sequence KDEL ensures transport of the protein into the endoplasmic reticulum and a retention therein, with the secretory proteins of KDEL sequence, the signal sequence is cleaved off by proteolysis in the ER, otherwise they will be retained inter alia, by the proteins KDELR1, 2 and 3.

Special

Some transmembrane proteins, the first transmembrane domain is also the signal sequence. Also referred to as a signal anchor sequence segment is characterized by a longer hydrophobic core region and a lack of Signalpeptidaseschnittstelle compared to the normal signal sequence.

The majority of proteins that are transported to the ER, has N- terminal-oriented signaling or signal anchor sequences. However, there are also integral membrane proteins that may be inserted without N -terminal signal sequence in the ER membrane. In these proteins, the recognition is located on a C-terminal hydrophobic segment. How these proteins insert into the ER membrane, but it is not clear so far.

Nucleus

Even when post-translational protein import into the cell nucleus is a signal sequence, here called nuclear localization signal, is required. This is a receptor recognized by nuclear import of this carried along in the core. The export of proteins from the nucleus takes place by means of a NES (german nuclear export signal) over Exportine and Ran -GTP with a G - protein - typical mechanism. The NES consists of the sequence with L LxxxLxxLxL representative of aliphatic amino acids such as leucine and x is any amino acid.

Mitochondrion

The protein import into the mitochondrion occurs post-translationally, ie after completion of protein biosynthesis. All import processes take place via the same transport machinery, the TOM complex ( English: translocase of the outer membrane ) of the outer mitochondrial membrane. There are also a number of other protein complexes that enable the integration of proteins into the outer mitochondrial membrane (SAM complex, sorting and assembly machinery ), import into the inner mitochondrial membrane and the mitochondrial matrix (TIM complexes, translocase of the inner membrane) mediate.

Protein precursors may be divided into two groups: the first group consists of proteins with N-terminal signals which are intended for the mitochondrial matrix, some of the inner membrane proteins, and the intermembrane space between outer and inner membrane. The amino acid residues carry positive charges and interact with the Importrezptoren organelle and guide it across the inner membrane to its destination. They generally consist of 20-40 amino acids, which form an amphiphilic α - helix, which is detected by the import apparatus. The signal sequence is truncated after the import by a peptidase.

The second group includes all outer membrane proteins, many proteins of the inner membrane and the intermembrane space. They only carry internal signals that can not be cut off.

Chloroplast

The protein import into chloroplasts occurs post-translationally via protein complexes TOC ( translocase of the outer chloroplast membrane) and TIC ( translocase of the inner chloroplast membrane).

Plastid Signal peptides are located at the N -terminus of the protein precursor and possess certain physical properties: they are rich in amino acids with hydroxylated residues have no acidic residues and do not form secondary structure. The presequence is phosphorylated and is one interactions with the proteins Hsp70 and 14-3-3, which accompany the protein to transport apparatus. After the import, the signal sequence is cut off by a peptidase. The outer membrane proteins require no N- terminal signal peptide, the mechanism of integration is still unknown.

Proteins whose destination is the membrane and the lumen of the thylakoids may also include additional signal sequences.

Peroxisome

The post-translational protein import into the peroxisome is based on two different types of signal sequences, called PTS1 and PTS2 (of English. Peroxisome targeting signal, such as " pointing to peroxisomes signals ").

PTS1 sequences are short, C -terminal signals that the amino acid sequence of (S / A / C) - included (L / L / M ) - ( K / R / H). They are recognized by the receptor peroxin -5 ( Pex5p ).

PTS2 sequences are signals from 9 amino acids located about 20 residues from the N- Terminus. The receptor for PTS2 signals is the peroxin -7 ( Pex7p ).