A look at the Tat system

In order for most proteins to relocate across membranes, they must unfold, take their journey and then refold upon reaching their destinations. However, in some situations, a protein needs to be translocated while remaining folded. This is the job of the Tat system.

In a recent minireview in the Journal of Biological Chemistry, Kenneth Cline of the University of Florida explores the mechanism of the Tat system. Tat, which stands for twin-arginine translocase, transports a variety of substrates of different sizes and types. The Tat system exists in various organisms and is present in some archaea and some mitochondria. Cline, however, focuses his review on research of the system in the thylakoid membranes of plant chloroplasts and in the cytoplasmic membrane of the E. coli bacterium.

Cline notes that the system has three components in both the thylakoid and in E. coli: TatA, TatB and TatC. The thylakoid orthologs of bacterial TatA and TatB are known as Tha4 and Hcf106 based on their genetic isolation, but the author indicates that the functions of these components are similar enough that this distinction is not necessary. He refers to them as TatA and TatB throughout the review. He also points out that the system’s presence in prokaryotes and prokaryote-derived organelles suggests that Tat has been around for quite some time.

The author highlights several important steps and players in the mechanism of Tat. He notes that the signal peptide has three parts: an amino proximal N domain, a hydrophobic H domain and a polar C domain that contains the signal peptidase cleavage site. At the N–H junction, however, lies the most important feature: the Arg-Arg (also known as RR) motif. This motif is not the entire consensus sequence, but the rest of the sequence varies among organisms and appears to be less important than the RR motif.

Cyclical mechanism for Tat protein transport. The TatBC receptor complex binds the substrate signal peptide in an energy-independent step. The receptor complex is depicted in the figure as a TatBC heterodimer, but it is actually a multimer estimated to contain up to 8 TatBC units. Signal peptide binding triggers PMF-dependent assembly and oligomerization of TatA. The resulting complex is the translocase. Changes in the TatA oligomer are thought to facilitate protein transport, after which the translocase dissociates.

Once the signal peptide targets the substrate, a cycle of substrate binding, translocase assembly and translocation occurs. The author explains that TatB and TatC are first present in equal amounts as a receptor complex. TatA is separate until the substrate signal peptide binds to the receptor complex, which then “triggers TatA assembly and oligomerization at the substrate-TatBC interface,” Cline writes. This complex is known as the translocase. Curiously, the order of the next steps is not known, but the author says they include transportation of the substrate, cleavage of signal peptide and disassembly of the TatA oligomer.

In the rest of the minireview, Cline delves deeper into the roles of TatA, TatB and TatC, and he offers details about how substrates bind and what that binding triggers. The author also goes into some aspects of the research that are not 100 percent certain. He discusses models for TatA-facilitated translocation and notes which model he thinks is best. He includes details regarding how the oligomeric TatBC structure may enable gated TatA assembly to form the translocase. He notes that mechanisms for how the protonmotive force and signal peptide binding act as triggers are still speculative.

In fact, Cline emphasizes that much of the information presented in the minireview is preliminary and is based on a single study. He believes that additional approaches will be necessary to create a detailed map of the subunit organization of TatABC and substrate as well as to gain an understanding of the interactions that regulate assembly of the translocase. The author reminds readers that this research is still at a relatively early stage. He goes on to propose some potential approaches for learning more, especially about how TatA assemblies enable passage of the substrate across the membrane, which he views as the core issue.

Photo of Alexandra Pantos Alexandra Pantos is an intern at the ASBMB and a senior biology student at the University of Maryland.