FIGURE 2.27 • Summary of events during protein synthesis. Proteins synthesis begins within the nucleus with transcription, during which the genetic code for a protein is transcribed from DNA to mRNA precursors. After post-transcriptional modifcations of the premRNA molecule—which include RNA cleavage, excision of introns, rejoining of exons, and capping by addition of poly(A) tracks at the 3 end and methylguanosine cap at the 5 end— the resulting mRNA molecule leaves the nucleus into the cytoplasm. In the cytoplasm, the mRNA sequence is read by the ribosomal complex in the process of translation to form a polypeptide chain. The frst group of 15 to 60 amino acids on the amino-terminus of a newly synthesized polypeptide forms a signal sequence (signal peptide) that directs protein to its destination (i.e., lumen of rER). The signal peptide interacts with a signal-recognition particle (SRP), which arrests further growth of the polypeptide chain until its relocation toward the rER membrane. Binding of THE SRP to a docking protein on the cytoplasmic surface of the rER aligns ribosome with the translocator protein. Binding of the ribosome to the translocator causes dissociation of the SRP–docking protein complex away from the ribosome, and protein synthesis is resumed. The translocator protein guides the polypeptide chain into the lumen of the rER cisterna. The signal sequence is cleaved from the polypeptide by signal peptidase and is subsequently digested by signal peptide peptidases. On completion of protein synthesis, the ribosome detaches from the translocator protein.
membrane. Binding of SRP to a docking protein on the cytoplasmic surface of rER aligns the ribosome with the translocator, an integral membrane protein of the rER. Binding of the ribosome to the protein translocator causes dissociation of the SRP–docking protein complex away from the ribosome and rER membrane, releasing the translational block and allowing the ribosome to resume protein synthesis (see Fig. 2.27). The translocator protein inserts the polypeptide chain into its aqueous pore, allowing newly formed protein to be discharged into the lumen of the rER cisterna. For simple secretory proteins, the polypeptide continues to be inserted by the translocator into the lumen as it is synthesized. The signal sequence is cleaved from the polypeptide by signal peptidase residing on the cisternal face of the rER membrane, even before the synthesis of the entire chain is completed. For integral membrane proteins, sequences along the polypeptide may instruct the forming protein to pass back and forth through the membrane, creating the functional domains that the protein will exhibit at its final membrane. On completion of protein synthesis, the ribosome detaches from the translocator protein and is again free in the cytoplasm.
The post-translational modification and sequestration of proteins within the rER is the first step in the exportation of proteins destined to leave the cell.
As polypeptide chains are synthesized by the membrane-bound polysomes, the protein is injected into the lumen of the rER cisterna, where it is further modified post-translationally by enzymes. These modifications include core glycosylation, disulfide-bond and internal hydrogen-bond formation, folding of the newly synthesized protein with the help of molecular chaperones, and partial subunit assembly. Proteins are then concentrated within a lumen of neighboring cisternae of rER, or they are carried to another part of the cell in the continuous channels of the rER.