Signal peptide

A signal peptide is a short (3-60 amino acids long) peptide chain that directs the transport of a protein. Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals.

There is some confusion relating to the precise meaning of the term 'signal peptide'. Some sources refer to signal peptides as only the pre-sequence that targets the propeptide to the endoplasmic reticulum and through the secretory pathway. Used in this system it does not refer to 'transit peptides'. A 'transit peptide' used in this system refers to the part of the pre-sequence that targets the protein to other organelles, such as mitochondria, chloroplasts and apicoplasts.

The amino acid sequences of signal peptides direct proteins (which are synthesized in the cytosol) to certain organelles such as the nucleus, mitochondrial matrix, endoplasmic reticulum, chloroplast, apoplast and peroxisome. Some signal peptides are cleaved from the protein by signal peptidase after the proteins are transported.

Endoplasmic reticulum
Almost all proteins that are transported to the endoplasmic reticulum have a sequence consisting of 5-10 hydrophobic amino acids on the N-terminus.

The protein is guided to the ER by a signal-recognition particle (SRP), which moves between the ER and the cytoplasm. It binds to the signal peptide. The SRP binds to the signal peptide as soon as it is synthesized and extruded from the ribosome. This causes a pause in protein synthesis, most probably allowing the ribosome-SRP complex time to bind to the SRP receptor on the target ER membrane. The SRP is thought to be a regulatory GTP protein. Conformational changes may therefore lead to the SRP release. The protein may then be threaded through the ER membrane by a translocator pore.

Most of these proteins are transported from the endoplasmic reticulum to the Golgi apparatus. If these proteins have a particular 4-amino-acid retention sequence, KDEL (lys-asp-glu-leu), on the C-terminus, they are retained in the endoplasmic reticulum or are routed back to the ER (in instances where they escape) via interaction with the KDEL receptor in the Golgi apparatus. Many records now,state that c-terminal KDEL in mammals, HDEL variants in yeast are conserved to be the re-router signals rather than ER retention signals.

Nucleus
A nuclear localization signal (NLS) is a signal peptide directing to the nucleus and is often a unit consisting of five basic, positively-charged amino acids. The NLS normally is located anywhere on the peptide chain.

Nucleolus
The nucleolus within the nucleus can be targeted with a sequence called a nucleolar localization signal (abbreviated NoLS or NOS).

Mitochondrial matrix
The signal peptide that directs to the mitochondrial matrix has a sequence consisting of an alternating pattern (amphipathic helix)with a few hydrophobic amino acids and a few positively charged amino acids at the N terminus. It is usually called the mitochondrial targeting signal (MTS).

Peroxisome
There are two types of signal peptides directing to peroxisome, which are called peroxisomal targeting signals (PTS). One is PTS1, which is made of three amino acids on the C-terminus. The other is PTS2, which is made of a 9-amino-acid sequence often present on the N-terminus of the protein.

Types
Following is a list of types of signal peptides:
 * N-terminus signal peptides often target the mitochondrial matrix, endoplasmic reticulum and peroxisome.
 * C-terminus signal peptides often target the peroxisome.

Examples of signal peptides
Transport to the nucleus (NLS)           -Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val- Transport to the endoplasmic reticulum   H2 N-Met-Met-Ser-Phe-Val-Ser-Leu- Leu-Leu-Val-Gly-Ile-Leu-Phe- Trp-Ala-Thr-Glu-Ala-Glu-Gln- Leu-Thr-Lys-Cys-Glu-Val-Phe- Gln- Retention to the endoplasmic reticulum   -Lys-Asp-Glu-Leu-COOH Transport to the mitochondrial matrix    H2N-Met-Leu-Ser-Leu-Arg-Gln-Ser- Ile-Arg-Phe-Phe-Lys-Pro-Ala- Thr-Arg-Thr-Leu-Cys-Ser-Ser- Arg-Tyr-Leu-Leu- Transport to the peroxisome (PTS1)       -Ser-Lys-Leu-COOH Transport to the peroxisome (PTS2)       H2N-Arg-Leu-X5-His-Leu- H2N is the N-terminus of a protein. COOH is the C-Terminus of a protein.