Biology
The components of the translocon and their functions are summarized in Figure 8.28. The simplicity of this system makes several important points. We visualize Sec61 as forming the channel and also as interacting with the ribosome. The initial targeting is made when the SRP recognizes the signal sequence as the newly synthesized protein begins to emerge from the ribosome. The SRP binds to the SRP receptor, and the signal sequence is transferred to the translocon. When the signal sequence enters the translocon, the ribosome attaches to Sec61, forming a seal so that the pore is not exposed to the cytosol. Cleavage of the signal peptide does not occur in this system, and therefore cannot be necessary for translocation per se. In this system, components on the lumenal side of the membrane are not needed for translocation.
- Anchor Sequences Determine Protein Orientation
KEY TERMS:An anchor (stop-transfer) (often referred to as a "transmembrane anchor") is a segment of a transmembrane protein which resides in the membrane. KEY CONCEPTS: An anchor sequence halts the passage of a protein through the translocon. Typically...
- Reverse Translocation Sends Proteins To The Cytosol For Degradation
KEY TERMS:Retrograde translocation (Reverse translocation) is the translocation of a protein from the lumen of the ER to the cytoplasm. It usually occurs to allow misfolded or damaged proteins to be degraded by the proteasome. KEY CONCEPTS: Sec61...
- The Signal Sequence Interacts With The Srp
KEY TERMS:Protein translocation describes the movement of a protein across a membrane. This occurs across the membranes of organelles in eukaryotes, or across the plasma membrane in bacteria. Each membrane across which proteins are translocated has a...
- Signal Sequences Initiate Translocation
KEY TERMS:Protein sorting (targeting) is the direction of different types of proteins for transport into or between specific organelles. A signal sequence is a short region of a protein that directs it to the endoplasmic reticulum for co-translational...
- Protein Translocation May Be Post-translational Or Co-translational
KEY TERMS:The leader of a protein is a short N-terminal sequence responsible for initiating passage into or through a membrane. A protein to be imported into an organelle or secreted from bacteria is called a "preprotein" until its signal sequence has...
Biology
Translocation requires insertion into the translocon and (sometimes) a ratchet in the ER
KEY CONCEPTS:
- The ribosome, SRP, and SRP receptor are sufficient to insert a nascent protein into a translocon.
- Proteins that are inserted post-translationally require additional components in the cytosol and Bip in the ER.
- Bip is a ratchet that prevents a protein from slipping backward.
The components of the translocon and their functions are summarized in Figure 8.28. The simplicity of this system makes several important points. We visualize Sec61 as forming the channel and also as interacting with the ribosome. The initial targeting is made when the SRP recognizes the signal sequence as the newly synthesized protein begins to emerge from the ribosome. The SRP binds to the SRP receptor, and the signal sequence is transferred to the translocon. When the signal sequence enters the translocon, the ribosome attaches to Sec61, forming a seal so that the pore is not exposed to the cytosol. Cleavage of the signal peptide does not occur in this system, and therefore cannot be necessary for translocation per se. In this system, components on the lumenal side of the membrane are not needed for translocation. Of course, the efficiency of the in vitro system is relatively low. Additional components could be required in vivo to achieve efficient transfer or to prevent other cellular proteins from interfering with the process (Gorlich and Rapoport, 1993; for review see Walter and Lingappa, 1986; Rapoport, Jungnickel, and Kutay, 1996).
A more complex apparatus is required in certain cases in which a protein is inserted into a membrane post-translationally. The same Sec61 complex forms the channel, but four other Sec proteins are also required, and in addition the chaperone BiP (a member of the Hsp70 class) and a supply of ATP are required on the lumenal side of the membrane. Figure 8.29 shows that BiP behaves as ratchet (Matlack et al., 1999). In the absence of BiP, Brownian motion allows the protein to slip back into the cytosol. But BiP grabs the protein as it exits the pore into the endoplasmic reticulum. This stops the protein from moving backward. BiP does not pull the protein through; it just stops it from sliding back. (The reason why BiP is required for post-translational translocation but not for co-translational translocation may be that a newly synthesized protein is continuously extruded from the ribosome and therefore cannot slip backward.)
- Anchor Sequences Determine Protein Orientation
KEY TERMS:An anchor (stop-transfer) (often referred to as a "transmembrane anchor") is a segment of a transmembrane protein which resides in the membrane. KEY CONCEPTS: An anchor sequence halts the passage of a protein through the translocon. Typically...
- Reverse Translocation Sends Proteins To The Cytosol For Degradation
KEY TERMS:Retrograde translocation (Reverse translocation) is the translocation of a protein from the lumen of the ER to the cytoplasm. It usually occurs to allow misfolded or damaged proteins to be degraded by the proteasome. KEY CONCEPTS: Sec61...
- The Signal Sequence Interacts With The Srp
KEY TERMS:Protein translocation describes the movement of a protein across a membrane. This occurs across the membranes of organelles in eukaryotes, or across the plasma membrane in bacteria. Each membrane across which proteins are translocated has a...
- Signal Sequences Initiate Translocation
KEY TERMS:Protein sorting (targeting) is the direction of different types of proteins for transport into or between specific organelles. A signal sequence is a short region of a protein that directs it to the endoplasmic reticulum for co-translational...
- Protein Translocation May Be Post-translational Or Co-translational
KEY TERMS:The leader of a protein is a short N-terminal sequence responsible for initiating passage into or through a membrane. A protein to be imported into an organelle or secreted from bacteria is called a "preprotein" until its signal sequence has...