When a signal sequence binds, SRP exposes a binding site for the SRP receptor (see Figure 12–36B,C), which is a transmembrane protein complex in the rough ER membrane. The binding of the SRP to its receptor brings the SRP–ribosome complex to an unoccupied protein translocator in the same membrane. The SRP and SRP receptor are then released, and the translocator transfers the growing polypeptide chain across the membrane (Figure 12–37).
This co-translational transfer process creates two spatially separate populations of ribosomes in the cytosol. Membrane-bound ribosomes, attached to the
Figure 12–37 How ER signal sequences and SRP direct ribosomes to the ER membrane. The srp and its receptor act in concert. The srp binds to both the exposed er signal sequence and the ribosome, thereby inducing a pause in translation. The srp receptor in the er membrane, which in animal cells is composed of two different polypeptide chains, binds the srp–ribosome complex and directs it to the translocator. in a poorly understood reaction, the srp and srp receptor are then released, leaving the ribosome bound to the translocator in the er membrane. The translocator then inserts the polypeptide chain into the membrane and transfers it across the lipid bilayer. Because one of the srp proteins and both chains of the srp receptor contain GTp-binding domains, it is thought that conformational changes that occur during cycles of GTp binding and hydrolysis (discussed in Chapter 15) ensure that srp release occurs only after the ribosome has become properly engaged with the translocator in the er membrane. The translocator is closed until the ribosome has bound, so that the permeability barrier of the er membrane is maintained at all times.
cytosolic side of the ER membrane, are engaged in the synthesis of proteins that are being concurrently translocated into the ER. Free ribosomes, unattached to any membrane, synthesize all other proteins encoded by the nuclear genome. Membrane-bound and free ribosomes are structurally and functionally identical. They differ only in the proteins they are making at any given time.
Since many ribosomes can bind to a single mRNA molecule, a polyribosome is usually formed. If the mRNA encodes a protein with an ER signal sequence, the polyribosome becomes attached to the ER membrane, directed there by the signal sequences on multiple growing polypeptide chains. The individual ribosomes associated with such an mRNA molecule can return to the cytosol when they finish translation and intermix with the pool of free ribosomes. The mRNA itself, however, remains attached to the ER membrane by a changing population of ribosomes, each transiently held at the membrane by the translocator (Figure 12–38).
The polypeptide Chain passes Through an aqueous Channel in the Translocator
It had long been debated whether polypeptide chains are transferred across the ER membrane in direct contact with the lipid bilayer or through a channel in a protein translocator. The debate ended with the identification of the translocator, which was shown to form a water-filled channel in the membrane through common pool of ribosomal subunits in cytosol mRNA encoding a protein targeted to ER remains membrane-bound