Abstract
ABSTRACTThe type II secretion system (T2SS) releases large folded exoproteins across the envelope of many Gram-negative pathogens. This secretion process therefore requires specific gating, interacting, and dynamics properties mainly operated by a bipartite outer membrane channel called secretin. We have a good understanding of the structure-function relationship of the pore-forming C-terminal domain of secretins. In contrast, the high flexibility of their periplasmic N-terminal domain has been an obstacle in obtaining the detailed structural information required to uncover its molecular function. In Pseudomonas aeruginosa, the Xcp T2SS plays an important role in bacterial virulence by its capacity to deliver a large panel of toxins and degradative enzymes into the surrounding environment. Here, we revealed that the N-terminal domain of XcpQ secretin spontaneously self-assembled into a hexamer of dimers independently of its C-terminal domain. Furthermore, and by using multidisciplinary approaches, we elucidate the structural organization of the XcpQ N domain and demonstrate that secretin flexibility at interdimer interfaces is mandatory for its function.
Highlights
IMPORTANCE Bacterial secretins are large homooligomeric proteins constituting the outer membrane pore-forming element of several envelope-embedded nanomachines essential in bacterial survival and pathogenicity
We previously showed that purified XcpQN interacts with secreted effectors and the inner membrane partner XcpP in a 1:1 stoichiometry [12]
Since XcpQN012 has a molecular mass of 26 kDa, we estimate that H and L complexes are homododecamers (12-mer) and homodimers (2-mer), respectively
Summary
IMPORTANCE Bacterial secretins are large homooligomeric proteins constituting the outer membrane pore-forming element of several envelope-embedded nanomachines essential in bacterial survival and pathogenicity. They comprise a well-defined membrane-embedded C-terminal domain and a modular periplasmic N-terminal domain involved in substrate recruitment and connection with inner membrane components. The C-terminal region, or -domain, is highly conserved among all secretins and formed by a giant 56- to 64--stranded pore constituted by the 14 to 16 4-stranded -sheets of each subunit [2,3,4] This domain forms the OM portal through which secreted substrates transit to the cell surface and is believed to be the major determinant in oligomer formation and stability [5, 6]. Secretin N domains play a direct role in secretion processes, since direct interactions have been reported with the secreted substrates [12, 17, 18] or the assembled pilus [17, 19]
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