Not only is the Sec61p translocon complex essential for translocation of proteins into the ER lumen, it also mediates the incorporation of integral membrane proteins into the ER membrane. The mechanism for integration is triggered by stop-transfer signals that cause a pause in translocation. Figure 31.5 shows the translocon as a closed cylinder spanning the membrane. Suggest a mechanism for lateral transfer of an integral membrane protein from the protein-conducting channel of the translocon into the hydrophobic phase of the ER membrane.

Proteins destined for the endoplasmic reticulum (ER) undergo a process called translocation, where they move across the ER membrane. This process is crucial for maintaining the function of cells, as the proteins serve a variety of roles once inside the ER, such as folding, modification, and sorting for transport to other areas of the cell.

The Sec61p translocon complex plays a pivotal role in this process. It acts as a gateway, allowing proteins to cross from the cytoplasm into the ER lumen or become part of the ER membrane itself. Translocation is initiated when a signal sequence on the nascent protein is recognized and bound by the signal recognition particle, which then docks to the translocon. The protein thread through the channel into the ER, where the signal sequence is often cleaved off upon entry.

Integral membrane proteins are those that are permanently attached to biological membranes, particularly the lipid bilayer of cells. Their integration into membranes is due to their hydrophobic regions, which interact favorably with the lipid tails within the membrane.

These proteins can serve as receptors, channels, or enzymes, and are vital for cellular communication and transport. To become part of the ER membrane, these proteins interact with the Sec61p translocon complex during their synthesis. Through specific signals and anchoring segments, they are inserted into the membrane in a way that orients their functional domains appropriately within the cell.

Stop-transfer signals play a critical role in the integration of integral membrane proteins. These are specific amino acid sequences within the protein being synthesized that halt the translocation process. When one of these signals is recognized by the translocon, it triggers the lateral release of the protein into the membrane, effectively integrating it as part of the ER membrane.

These signals are composed of hydrophobic amino acids which interact with the lipid environment of the membrane, allowing the protein to become part of it without fully entering the ER lumen. This selective pausing is an elegant way the cell uses to correctly position membrane proteins.

The protein-conducting channel, often referred to as the translocon, is a complex, gated passageway through which nascent proteins enter the ER. It is essential for protein translocation and is highly dynamic in nature, responding to various signals that regulate its opening and closing.

When the stop-transfer sequence of an integral membrane protein arrives at the translocon, the channel alters its conformation. This change allows the protein to exit sideways into the lipid bilayer rather than continuing into the ER lumen. This lateral gating mechanism is crucial for the proper placement of integral membrane proteins.

The mechanism of protein integration into the ER membrane involves a choreographed interaction between the nascent protein, the Sec61p translocon complex, and the membrane itself. When the elongating peptide reaches a stop-transfer signal, the translocon recognizes this sequence and opens laterally towards the lipid bilayer.

This action is akin to a side door on the translocon opening, allowing the hydrophobic region of the protein to slip into the lipid phase of the membrane. The protein can then fold properly with portions that remain functional within the ER, on its surface, or extruding into the cytoplasm. Thus, the stop-transfer signal effectively acts as a 'bookmark', indicating where the protein should reside within the cellular architecture.