Signal recognition particle
Encyclopedia
The signal recognition particle (SRP) is an abundant, cytosolic, universally conserved ribonucleoprotein
(protein
-RNA
complex) that recognizes and targets specific proteins to the endoplasmic reticulum
in eukaryote
s and the plasma membrane in prokaryote
s.
s, newly synthesized proteins in eukaryotes carry N-terminal hydrophobic signal sequence
s, which are bound by SRP when they emerge from the ribosome
.
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
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
, in the ER (Endoplasmic reticulum
) 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 prerequiste 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.
), with GTPase
activity. The components of the complex are:
The prokaryotic SRP is composed of one polypeptide bound to an RNA molecule (the 4.5S RNA
), with GTPase
activity. The components of the complex are:
Ffh is the structural and functional homolog of the SRP54 protein in eukaryotes. The 4.5S RNA shares sequence and structural homology with one domain of the larger 7S RNA.
. For individuals with polymyositis, the presence of anti-SRP antibodies are associated with more prominent muscle weakness and atrophy.
Ribonucleoprotein
Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
(protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
-RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
complex) that recognizes and targets specific proteins to the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
in eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s and the plasma membrane in prokaryote
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
s.
History
The function of SRP was discovered by the study of processed and unprocessed immunoglobulin light chainImmunoglobulin light chain
]The immunoglobulin light chain is the small polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains.-In humans:...
s, newly synthesized proteins in eukaryotes carry N-terminal hydrophobic signal sequence
Signal sequence
Signal sequence can refer to:*Protein targeting*Signal peptide*DNA uptake signal sequence...
s, which are bound by SRP when they emerge from the ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
.
Mechanism
In eukaryotes, SRP binds to the signal sequenceSignal sequence
Signal sequence can refer to:*Protein targeting*Signal peptide*DNA uptake signal sequence...
of a newly synthesized peptide as it emerges from the ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
. 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 (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
and the protein translocation processes. SRP then targets this entire complex (the ribosome-nascent chain complex
Ribosome Nascent chain Complex
Ribosome-Nascent chain Complex is the term used to refer to the collection of molecules that constitute a ribosome attached to the polypeptide that it is synthesising. The synthesis of the nascent polypeptide may be stalled by one of several methods...
) to the protein-conducting channel, also known as the translocon
Translocon
The translocon is the complex of proteins associated with the translocation of nascent polypeptides across membranes. In eukaryotes the polypeptides are transported into the interior space of the endoplasmic reticulum from the cytosol...
, in the ER (Endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
) 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 triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
(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 prerequiste 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 peptidase
Signal peptidases are enzymes that convert secretory and some membrane proteins to their mature form by cleaving off their N-terminal targeting signals....
. Signal sequences are therefore not a part of mature proteins.
The composition of SRP
Despite SRP function being analogous in all organisms, its composition varies greatly. The eukaryotic SRP is composed of six distinct polypeptides bound to an RNA molecule (the 7SL RNASignal recognition particle RNA
The signal recognition particle RNA, also known as 7SL, 6S, , or 4.5S RNA, is the RNA component of the signal recognition particle ribonucleoprotein complex. SRP is a universally conserved ribonucleoprotein that directs the traffic of proteins within the cell and allows them to be secreted...
), with GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
activity. The components of the complex are:
- SRP9
- SRP14
- SRP19
- SRP54
- SRP68
- SRP72
- SRP RNASignal recognition particle RNAThe signal recognition particle RNA, also known as 7SL, 6S, , or 4.5S RNA, is the RNA component of the signal recognition particle ribonucleoprotein complex. SRP is a universally conserved ribonucleoprotein that directs the traffic of proteins within the cell and allows them to be secreted...
The prokaryotic SRP is composed of one polypeptide bound to an RNA molecule (the 4.5S RNA
Signal recognition particle RNA
The signal recognition particle RNA, also known as 7SL, 6S, , or 4.5S RNA, is the RNA component of the signal recognition particle ribonucleoprotein complex. SRP is a universally conserved ribonucleoprotein that directs the traffic of proteins within the cell and allows them to be secreted...
), with GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
activity. The components of the complex are:
- Ffh
- 4.5S RNA
Ffh is the structural and functional homolog of the SRP54 protein in eukaryotes. The 4.5S RNA shares sequence and structural homology with one domain of the larger 7S RNA.
Autoantibodies
Anti-signal recognition particle antibodies are mainly associated with, but are not very specific for, polymyositisPolymyositis
Polymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:...
. For individuals with polymyositis, the presence of anti-SRP antibodies are associated with more prominent muscle weakness and atrophy.
External links
- Signal Recognition Particle Database
- www.dnaTube.com video showing an SRP in action
- Another SRP video at www.dnaTube.com
- The Nobel Prize in Physiology or Medicine 1999, "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