The translocon (also called a translocator or translocation channel) is a general term for a protein channel in biological membranes that functions to move polypeptides across the membrane or insert them into the lipid bilayer. This structure is a key component of the protein translocation pathway in all organisms, from bacteria, archaea, and eukaryotes. In eukaryotes the term translocon most commonly refers to the complex that transports nascent polypeptides with a targeting signal sequence from the cytosol into the interior (cisternal or lumenal) space of the endoplasmic reticulum (ER). This translocation process requires the protein to cross a hydrophobic lipid bilayer. In prokaryotes, a similar protein complex transports polypeptides across the (inner) plasma membrane or integrates membrane proteins. In either case, the protein complex is formed from Sec proteins (Sec: secretory), with the hetero-trimeric Sec61 being the channel. In prokaryotes, the homologous channel complex is known as SecYEG.
Structure and component The translocon typically consists of integral membrane proteins that form a narrow channel, just wide enough for an unfolded polypeptide chain to pass through. The core structure of the translocon varies depending on the system:
Sec System Prokaryotes: SecYEG complex Eukaryotes: Sec61αβγ complex TAT System (Twin-Arginine Translocation) TatA, TatB, TatC complex, specialized for fully folded proteins YidC System Inserts membrane proteins without passing through the Sec pathway Translocons often have a “lateral gate” that allows hydrophobic segments (transmembrane domains) to exit directly into the lipid bilayer.
Central channel
The structure of this channel in its inactive state has been determined in archaea using X-ray crystallography. In cells, the translocon channel is a three-part protein complex known as SecYEG in prokaryotes and Sec61 in eukaryotes. It is made up of the subunits SecY, SecE, and SecG, with SecY forming the main pore. The structure of this channel, in its idle state, has been solved by X-ray crystallography in archaea. In some cases, the core trimer joins with four additional proteins to form a larger seven-part (heptameric) complex, which is responsible for transporting certain polypeptides into the endoplasmic reticulum (ER). The channel has a distinctive hourglass shape when viewed from the side, with a funnel at both ends. The funnel facing outside the cell or organelle is closed by a small “plug” made of an alpha-helix. In the middle of the membrane is a ring of six hydrophobic amino acids whose side chains point inward, forming a selective barrier. When protein translocation begins, the plug moves aside, and the new polypeptide chain passes from the cytoplasmic funnel, through the pore ring, and out through the opposite funnel. For membrane proteins, hydrophobic regions exit through a side opening called the lateral gate, entering the surrounding lipid layer and becoming segments that span the membrane.
Associated protein In bacteria, SecYEG forms a complex with SecDF, YajC and YidC. In eukaryotes, Sec61 forms a complex with the oligosaccharyl transferase complex, the TRAP complex, and the membrane protein TRAM (possible chaperone). For further components, such as signal peptidase complex and the SRP receptor it is not clear to what extent they only associate transiently to the translocon complex.
Translocation mechanism The translocon channel can let peptides move in either direction, so it needs additional components to push the peptide the right way. There are two main types of translocation: co-translational, which happens while the protein is still being made by the ribosome, and post-translational, which takes place after the protein is completed. Both processes occur in eukaryotes and bacteria, but the mechanisms differ. In eukaryotes, proteins are moved with the help of BiP and other transport complexes, while in bacteria, the SecA ATPase provides the energy to push the peptide through the channel.
Co-translational translocation
In co-translational translocation, the translocon works together with the ribosome so that a growing protein chain moves directly from the ribosome into the translocon channel. In eukaryotes, this process begins when a signal recognition particle (SRP) identifies a short signal sequence at the start of the protein. The SRP pauses protein synthesis and directs the ribosome to the SRP receptor on the endoplasmic reticulum (ER). Once the ribosome is attached, the SRP is released, and protein synthesis resumes. The new protein is threaded through the Sec61 channel in an unfolded form, sometimes with the help of a mechanism known as a Brownian Ratchet. After the protein is fully made, a signal peptidase cuts off the short signal sequence, releasing the finished protein into the ER’s interior. The ER translocon is a group of connected protein complexes, including Sec61 (the channel), the TRAP complex, and the oligosaccharyl transferase (OST) complex, which can attach sugar molecules to the new protein as it enters the ER. Bacteria use a similar SRP system, along with a chaperone called YidC, which is comparable to the TRAM protein in eukaryotes. The translocon can also insert membrane proteins into the ER membrane in the correct orientation. This depends on recognizing hydrophobic parts of the protein sequence that will become transmembrane helices. These helices are positioned by the translocon through a combination of stop-transfer and signal sequences, with the channel’s plug opening and closing to place them properly in the membrane.
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