Figure 12–38 Free and membrane-bound polyribosomes. (a) a common pool of ribosomes synthesizes the proteins that stay in the cytosol and those that are transported into the er. The er signal sequence on a newly formed polypeptide chain binds to srp, which directs the translating ribosome to the er membrane. The mrna molecule remains permanently bound to the er as part of a polyribosome, while the ribosomes that move along it are recycled; at the end of each round of protein synthesis, the ribosomal subunits are released and rejoin the common pool in the cytosol. (B) a thin section electron micrograph of polyribosomes attached to the er membrane. The plane of section in some places cuts through the er roughly parallel to the membrane, giving a face-on view of the rosettelike pattern of the polyribosomes. (B, courtesy of George palade.)
Figure 12–39 Structure of the Sec61 complex. (a) a side view (left) and a top view (right, seen from the cytosol) of the structure of the sec61 complex of the archaeon Methanococcus jannaschii. The sec61α subunit has an inverted repeat structure (see figure 11–10) and is shown in blue and beige to indicate this pseudo-symmetry; the two smaller β and γ subunits are shown in gray. in the side view, some helices in front have been omitted to make the inside of the pore visible. The yellow short helix is thought to form a plug that seals the pore when the translocator is closed. To open, the complex rearranges itself to move the plug helix out of the way, as indicated by the red arrow. a ring of hydrophobic amino acid side chains is thought to form a tight-fitting diaphragm around translocating polypeptide chain to prevent leaks of other molecules across the membrane. The pore of the sec61 complex can also open sideways at a lateral seam. (B) models of the closed and open states of the translocator are shown in top view, illustrating how a signal sequence (or a transmembrane segment) could be released into the lipid bilayer after opening of the seam. (pDB codes: 1rh5 and 1rhz.) which the polypeptide chain passes. The core of the translocator, called the Sec61 complex, is built from three subunits that are highly conserved from bacteria to eukaryotic cells. The structure of the Sec61 complex suggests that α helices contributed by the largest subunit surround a central channel through which the polypeptide chain traverses the membrane (Figure 12–39). The channel is gated by a short α helix that is thought to keep the translocator closed when it is idle and to move aside when it is engaged in passing a polypeptide chain. According to this view, the pore is a dynamic gated channel that opens only transiently when a polypeptide chain traverses the membrane. In an idle translocator, it is important to keep the channel closed, so that the membrane remains impermeable to ions, such as Ca2+, which otherwise would leak out of the ER. As a polypeptide chain is translocating, a ring of hydrophobic amino acid side chains is thought to provide a flexible seal to prevent ion leaks.
The structure of the Sec61 complex suggests that the pore can also open along a seam on its side. Indeed, some structures of the translocator show it locked in an open-seam conformation. This opening allows a translocating peptide chain lateral access into the hydrophobic core of the membrane, a process that is important both for the release of a cleaved signal peptide into the membrane (see Figure 12–35) and for the integration of transmembrane proteins into the bilayer, as we discuss later.