title: Linked domain architectures allow for specialization of function in the FtsK/SpoIIIE ATPases of ESX secretion systems.
abstract: Among protein secretion systems, there are specialized ATPases that serve different functions such as substrate recognition, substrate unfolding, and assembly of the secretory machinery. ESX (early secretory antigen target 6 kDa secretion) protein secretion systems require FtsK/SpoIIIE family ATPases but the specific function of these ATPases is poorly understood. The ATPases of ESX secretion systems have a unique domain architecture among proteins of the FtsK/SpoIIIE family. All well-studied FtsK family ATPases to date have one ATPase domain and oligomerize to form a functional molecular machine, most commonly a hexameric ring. In contrast, the ESX ATPases have three ATPase domains, encoded either by a single gene or by two operonic genes. It is currently unknown which of the ATPase domains is catalytically functional and whether each domain plays the same or a different function. Here we focus on the ATPases of two ESX systems, the ESX-1 system of Mycobacterium tuberculosis and the yuk system of Bacillus subtilis. We show that ATP hydrolysis by the ESX ATPase is required for secretion, suggesting that this enzyme at least partly fuels protein translocation. We further show that individual ATPase domains play distinct roles in substrate translocation and complex formation. Comparing the single-chain and split ESX ATPases, we reveal differences in the requirements of these unique secretory ATPases.
authors: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors: Talia L
authors: TL
authors: Ramsdell
authors: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors: Laura A
authors: LA
authors: Huppert
authors: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors: Tatyana A
authors: TA
authors: Sysoeva
authors: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: sfortune@hsph.harvard.edu.
authors: Sarah M
authors: SM
authors: Fortune
authors: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: bburton@mcb.harvard.edu.
authors: Briana M
authors: BM
authors: Burton
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000378:metabolism; D001412:Bacillus subtilis / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D016415:Sequence Alignment
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C030069:spore-specific proteins, Bacillus; D000251:Adenosine Triphosphatases
keywords: ESX secretion; FtsK-like ATPases; mycobacterial protein secretion; secretory ATPases; type VII secretion system