Monday's Molecule #44 is

signal recognition particle or SRP. The figure is a model of SRP (red) bound to a
ribosome at the exit site of the tunnel in the large subunit (white asterisk)
(Schaffitzel et al. 2006). In the right-hand version of the model you can see
that SRP is made up of an RNA molecule and associated proteins.

Signal recognition particle is an important component of the secretory pathway.

The mechanism of secretion in response to a signal on the growing polypeptide
is known as the Signal Hypothesis. Here's how we describe it in our
textbookPrinciples of Biochemistry 4/e.

Secreted proteins are synthesized on the surface of the endoplasmic reticulum,

and the newly synthesized protein is passed through the membrane into the
lumen. In cells that make large amounts of secreted protein, the endoplasmic
reticulum membranes are covered with ribosomes.

The clue to the process by which many proteins cross the membrane of the
endoplasmic reticulum appears in the first 20 or so residues of the nascent
polypeptide chain. In most membrane-bound and secreted proteins, these
residues are present only in the nascent polypeptide, not in the mature protein.
The N-terminal sequence of residues that is proteolytically removed from the
protein precursor is called the signal peptide since it is the portion of the
precursor that signals the protein to cross a membrane. Signal peptides vary in
length and composition, but they are typically from 16 to 30 residues long and
include 4 to 15 hydrophobic residues.
 In eukaryotes, many proteins destined for secretion
appear to be translocated across the endoplasmic reticulum by the pathway
shown in the Figure. In the first step, an 80S initiation complex—including a
ribosome, a Met-tRNAiMetmolecule, and an mRNA molecule—forms in the cytosol.
Next, the ribosome begins translating the mRNA and synthesizing the signal
peptide at the N-terminus of the precursor. Once the signal peptide has been
synthesized and extruded from the ribosome, it binds to a protein-RNA complex
called a signal recognition particle (SRP).

SRP is a small ribonucleoprotein containing a 300-nucleotide RNA molecule

called 7SL RNA and four proteins. SRP recognizes and binds to the signal
peptide as it emerges from the ribosome. When SRP binds, further translation is
blocked. The SRP-ribosome complex then binds to an SRP receptor protein (also
known as docking protein) on the cytosolic face of the endoplasmic reticulum.
The ribosome is anchored to the membrane of the endoplasmic reticulum by
ribosome-binding proteins called ribophorins, and the signal peptide is inserted
into the membrane at a pore that is part of the complex formed by the
endoplasmic reticulum proteins at the docking site.
 Once the ribosome-SRP complex is bound to the membrane,
the inhibition of translation is relieved and SRP dissociates in a reaction coupled
to GTP hydrolysis. Thus, the role of SRP is to recognize nascent polypeptides
containing a signal peptide and to target the translation complex to the surface
of the endoplasmic reticulum.

Once the translation complex is bound to the membrane, translation resumes

and the new polypeptide chain passes through the membrane. The signal
peptide is then cleaved from the nascent polypeptide by a signal peptidase, an
integral membrane protein associated with the pore complex. The transport of
proteins across the membrane is assisted by chaperones in the lumen of the
endoplasmic reticulum. In addition to their role in protein folding, chaperones
are required for translocation, and their activity requires ATP hydrolysis. When
protein synthesis terminates, the ribosome dissociates from the endoplasmic
reticulum, and the translation complex disassembles