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 int ...

(

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, res ...

- RNA complex) that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in

prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Conne ...

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.

Mechanism

In eukaryotes, SRP binds to the signal sequence of a newly synthesized peptide as it emerges from the ribosome. 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 of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

and the

protein translocation :''This article deals with protein targeting in eukaryotes unless specified otherwise.'' Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the ce ...

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 Signal recognition particle (SRP) receptor, also called the docking protein, is a dimer composed of 2 different subunits that are associated exclusively with the rough ER in mammalian cells. Its main function is to identify the SRP units. SRP ( ...

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 d ...

(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 The signal recognition particle RNA, (also known as 7SL, 6S or 4.5S RNA) is part of the signal recognition particle (SRP) ribonucleoprotein complex. SRP recognizes the signal peptide and binds to the ribosome, halting protein synthesis. Signal re ...

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 pro ...

activity is shared in all cellular life, but some subunit

polypeptides Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

are specific to eukaryotes.

Autoantibodies and disease

Anti-signal recognition particle antibodies Inflammatory myopathy is disease featuring weakness and inflammation of muscles and (in some types) muscle pain. The cause of much inflammatory myopathy is unknown (idiopathic), and such cases are classified according to their symptoms and signs ...

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 means "inflammation of many muscles" ('' poly-'' + '' myos-'' + '' -itis''). The inflam ...

. 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