Mixed findings on the structure of a channel for moving proteins across membranes have been clarified by HMS cell biologists. The researchers discovered that while multiple units make up the channel, the actual pore through which proteins travel is formed from a single unit in the complex. The study, reported in the April 6 Cell, describes a basic mechanism of cellular protein translocation.
In eukaryotic cells, secreted proteins must be translocated across the membrane of the endoplasmic reticulum before they are trafficked out of the cell. A similar system exists in bacterial cells, except that secreted proteins are translocated directly across the plasma membrane. In both cases, translocation is mediated by a conserved protein-conducting channel, and these channels are formed by the protein complexes SecY and Sec61 in eukaryotes and in bacteria, respectively.
But the exact nature of the protein-conducting channels has been murky. Some studies have suggested that a single SecY/Sec61 complex is sufficient to form a translocation channel while others have suggested that multiple SecY/Sec61 complexes collaborate to form a much larger channel. Using E. coli, Tom Rapoport, HMS professor of cell biology, and Andrew Osborne, a research fellow, identified a fraternal twin–like arrangement in which the channel possesses two SecY units, each one taking on a different function.
Using cross-linking approaches, Rapoport and Osborne found that the pore of the channel was contained within one SecY complex. Yet further experiments showed that SecY complexes, indeed, oligomerize. While the first SecY complex forms the actual pore, the second one makes a binding site for the cytoplasmic ATPase SecA, which facilitates protein translocation in bacteria. “The translocation motor SecA binds with one of its domains to a non-translocating SecY copy and pushes the polypeptide chain through a neighboring SecY copy,” Rapoport explained.
The findings suggest that while the SecY channel is indeed formed from an oligomeric assembly of more than one SecY complex, the pore of the channel is contained within a single SecY copy. “What is interesting about this model is that we have a homodimer—two SecYs—but they are not identical,” Rapoport said.
The findings indicate a division of labor between the SecY copies, resolving a puzzle about the size and makeup of the pore. Because SecA appears essential in this model of translocation—and is unique to bacteria—the protein is a potential antibacterial target.
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