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

ribonucleoprotein Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating inter ...

(

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

complex) that recognizes and targets specific proteins to the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

s and the

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

prokaryote A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...

History

The function of SRP was discovered by the study of processed and unprocessed secretory proteins, particularly

immunoglobulin light chain ] The immunoglobulin light chain is the small Peptide, polypeptide subunit of an antibody (immunoglobulin). A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two Ig light chains. In humans There are two types of light ...

s; and bovine preprolactin. Newly synthesized proteins in eukaryotes carry N-terminal hydrophobic Signal peptide, signal sequences, which are bound by SRP when they emerge from the

ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

Mechanism

eukaryotes The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of ...

, 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 semantics, 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 English la ...

and the

protein translocation Protein targeting or protein sorting is the Mechanism (biology), biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, diffe ...

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 transpor ...

, in the

(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 Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription process. Its structure is similar to that of the guanosine nucleoside, the only di ...

(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 peptidases are enzymes that convert secretory and some membrane proteins to their mature or pro forms by cleaving their signal peptides from their N-termini. Signal peptidases were initially observed in endoplasmic reticulum (ER)-deri ...

. 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 GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...

activity is shared in all cellular life, but some subunit

polypeptides Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ami ...

are specific to eukaryotes.

Autoantibodies and disease

Anti-signal recognition particle antibodies Inflammatory myopathy, also known as idiopathic inflammatory myopathy (IIM), is disease featuring muscle weakness, inflammation of muscles ( myositis), and in some types, muscle pain ( myalgia). The cause of much inflammatory myopathy is unknown ...

are mainly associated with, but are not very specific for,

polymyositis Polymyositis (PM) is a type of chronic inflammation of the muscles ( inflammatory myopathy) related to dermatomyositis and inclusion body myositis. Its name is derived . The inflammation of polymyositis is mainly found in the endomysial layer ...

. 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