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 way it does not refer to 'transit peptides'^[1]. A 'transit peptide' used in this way 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.

Types by protein destination

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 protein 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.

Nucleus

A nuclear localization signal (NLS) is a signal peptide directing to the nucleus and is often a unit consisting of plus-charged amino acids. The NLS normally is located inside 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 with a few hydrophobic amino acids and a few plus-charged amino acids form. 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    H2N-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.

See also

• Protein targeting

References

1. ^ Olof Emanuelsson, Søren Brunak, Gunnar von Heijne, Henrik Nielsen (2007). "Locating proteins in the cell using TargetP, SignalP, and related tools". Nature Protocols 2: 953–971. PMID 17446895. 

External links

• MeSH Signal+Peptide
• SPdb (Signal Peptide DataBase)
• SignalP — predicts the presence and location of signal peptide cleavage sites in amino acid sequences from different organisms.