title: PilMNOPQ from the Pseudomonas aeruginosa type IV pilus system form a transenvelope protein interaction network that interacts with PilA.
abstract: Pseudomonas aeruginosa type IV pili (T4P) are virulence factors that promote infection of cystic fibrosis and immunosuppressed patients. As the absence of T4P impairs colonization, they are attractive targets for the development of novel therapeutics. Genes in the pilMNOPQ operon are important for both T4P assembly and a form of bacterial movement, called twitching motility, that is required for pathogenicity. The type II membrane proteins, PilN and PilO, dimerize via their periplasmic domains and anchor this complex in the inner membrane. Our earlier work showed that PilNO binds PilP, a periplasmic lipoprotein (S. Tammam, L. M. Sampaleanu, J. Koo, P. Sundaram, M. Ayers, P. A. Chong, J. D. Forman-Kay, L. L. Burrows, and P. L. Howell, Mol. Microbiol. 82:1496-1514, 2011). Here, we show that PilP interacts with the N0 segment of the outer membrane secretin PilQ via its C-terminal domain, and that the N-terminal cytoplasmic tail of PilN binds to the actin-like protein PilM, thereby connecting all cellular compartments via the PilMNOPQ protein interaction network. We show that PilA, the major pilin subunit, interacts with PilNOPQ. The results allow us to propose a model whereby PilA makes extensive contacts with the transenvelope complex, possibly to increase local concentrations of PilA monomers for polymerization. The PilNOP complex could provide a stable anchor in the inner membrane, while the PilMNOPQ transenvelope complex facilitates transit of the pilus through the periplasm and clamps the pilus in the cell envelope. The PilMN interaction is proposed to be responsible for communicating signals from the cytoplasmic to periplasmic components of this complex macromolecular machine.
authors: Program in Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Stephanie
authors: S
authors: Tammam
authors: Liliana M
authors: LM
authors: Sampaleanu
authors: Jason
authors: J
authors: Koo
authors: Kumararaaj
authors: K
authors: Manoharan
authors: Mark
authors: M
authors: Daubaras
authors: Lori L
authors: LL
authors: Burrows
authors: P Lynne
authors: PL
authors: Howell
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D036781:Fimbriae Proteins