Structure of a pilin monomer from Pseudomonas aeruginosa: implications for the assembly of pili.
Type IV pilin monomers assemble to form fibers called pili that are required for a variety of bacterial functions. Pilin monomers oligomerize due to the interaction of part of their hydrophobic N-terminal alpha-helix. Engineering of a truncated pilin from Pseudomonas aeruginosa strain K122-4, where the first 28 residues are removed from the N terminus, yields a soluble, monomeric protein. This truncated pilin is shown to bind to its receptor and to decrease morbidity and mortality in mice upon administration 15 min before challenge with a heterologous strain of Pseudomonas. The structure of this truncated pilin reveals an alpha-helix at the N terminus that lies across a 4-stranded antiparallel beta-sheet. A model for a pilus is proposed that takes into account both electrostatic and hydrophobic interactions of pilin subunits as well as previously published x-ray fiber diffraction data. Our model indicates that DNA or RNA cannot pass through the center of the pilus, however, the possibility exists for small organic molecules to pass through indicating a potential mechanism for signal transduction.
Keizer
D W
DW
Protein Engineering Network Centres of Excellence (PENCE), 713 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Slupsky
C M
CM
Kalisiak
M
M
Campbell
A P
AP
Crump
M P
MP
Sastry
P A
PA
Hazes
B
B
Irvin
R T
RT
Sykes
B D
BD
D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000627:therapeutic use*; D001428:Bacterial Vaccines; D001667:Binding, Competitive; D004311:Double-Blind Method; D036781:Fimbriae Proteins; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000627:therapeutic use; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary; D011552:Pseudomonas Infections / Q000628:therapy; D011550:Pseudomonas aeruginosa / Q000276:immunology; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015996:Survival Rate
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D008565:Membrane Proteins; D010446:Peptide Fragments; C432413:type IV pilin (29-150), Pseudomonas aeruginosa, K122-4 strain; D036781:Fimbriae Proteins