Most proteins are inserted into the ER by a ribosome before the synthesis of their polypeptide chains has completed. This is a co-translational process. According to the signal hypothesis (Alberts et al 2008, p.727), all proteins are directed to the ER by a signal sequence that the ribosome synthesises using mRNA and the signal sequence gives the protein an extra length called the N-terminal leader peptide. The signal sequence is recognised by a signal recognition particle (SRP) as soon as it emerges from the ribosome.
The SRP consists of six polypeptide chains associated with a short length of RNA and it travels from the ER to the incoming ribosome to bind the signal sequence using a hydrophobic pocket consisting of non-polar amino acids, such as Methionines. The non-polar amino acids help the hydrophobic pocket to flex and accommodate the lengths of different signal sequences. The SRP also binds the elongation factor binding site on the ribosome to halt the synthesis of the polypeptide as soon as it emerges from the ribosome to give the SRP a chance to guide the polypeptide to the ER. This prevents the completion of protein synthesis before it has a chance to enter the ER. The SRP then binds to a SRP receptor on the surface of the rough ER and, it is proposed (Karp 2010, p.458), that the signal sequence on the polypeptide opens a water filled pore in the ER membrane called a translocon, through which the polypeptide chain is inserted by the ribosome. The translocon core is presently considered to consist of a complex called Sec61 (Alberts et al 2008, p.730). The SRP and SRP receptor are released back into the cytosol once the ribosome starts inserting the protein into the ER. The ribosome then continues translation of the mRNA to form the protein. Within the ER luminal space the signal sequence on the peptide is cleaved by a signal peptidase.
The Slideshow above shows the process of co-translational transport. Click the arrows to see the process.
Post- translational Transport
In some Eukaryotes, such as yeast, post-translational transport occurs (Alberts et al 2008, p. 731). This is where a protein is completely translated in the cytosol by a ribosome and then imported into the ER by a translocon. In this process the finished protein is bound in the cytosol by chaperone proteins, which prevent folding of the newly synthesised protein, and then guided and inserted into the translocon pore by additional complexes. The protein is pulled through the aqueous pore by Binding Protein molecules (BiP) that use ATP driven cycles to import protein into the ER lumen.