The signal recognition particle (SRP) is an abundant, cytosolic, universally conserved ribonucleoprotein (

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

complex) that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

in prokaryotes.

History

The function of SRP was discovered by the study of processed and unprocessed secretory proteins, particularly immunoglobulin light chains; and bovine preprolactin. Newly synthesized proteins in eukaryotes carry N-terminal hydrophobic signal sequences, which are bound by SRP when they emerge from the

ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...

Mechanism

In eukaryotes, SRP binds to the signal sequence of a newly synthesized peptide as it emerges from the

. This binding leads to the slowing of protein synthesis known as "elongation arrest", a conserved function of SRP that facilitates the coupling of the protein

translation Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...

and the protein translocation processes. SRP then targets this entire complex (the ribosome-nascent chain complex) to the protein-conducting channel, also known as the

translocon The translocon (also known as a translocator or translocation channel) is a complex of proteins associated with the translocation of polypeptides across membranes. In eukaryotes the term translocon most commonly refers to the complex that transport ...

, in the endoplasmic reticulum (ER) membrane. This occurs via the interaction and docking of SRP with its cognate SRP receptor that is located in close proximity to the translocon. In eukaryotes there are three domains between SRP and its receptor that function in guanosine triphosphate (GTP) binding and hydrolysis. These are located in two related subunits in the SRP receptor (SRα and SRβ) and the SRP protein SRP54 (known as Ffh in bacteria). The coordinated binding of GTP by SRP and the SRP receptor has been shown to be a prerequisite for the successful targeting of SRP to the SRP receptor. Upon docking, the nascent peptide chain is inserted into the translocon channel where it enters into the ER. Protein synthesis resumes as SRP is released from the ribosome. The SRP-SRP receptor complex dissociates via GTP hydrolysis and the cycle of SRP-mediated protein translocation continues. Once inside the ER, the signal sequence is cleaved from the core protein by signal peptidase. Signal sequences are therefore not a part of mature proteins.

Composition and evolution

Despite SRP function being analogous in all organisms, its composition varies greatly. The SRP54- SRP RNA core with GTPase activity is shared in all cellular life, but some subunit polypeptides are specific to eukaryotes.

Autoantibodies and disease

Anti-signal recognition particle antibodies are mainly associated with, but are not very specific for, polymyositis. For individuals with polymyositis, the presence of anti-SRP antibodies are associated with more prominent muscle weakness and atrophy.

References

External links

*
Signal Recognition Particle Database

www.dnaTube.com video showing an SRP in action

Another SRP video at www.dnaTube.com

"for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell" to Günter Blobel, USA. Press Release, Illustrated Presentation, Presentation Speech {{Ribonucleoproteins Cell signaling