A molecular dynamics study of pilus subunits: insights into pilus biogenesis

J Mol Biol. 2007 Apr 6;367(4):935-41. doi: 10.1016/j.jmb.2007.01.034. Epub 2007 Jan 20.

Abstract

Biogenesis of pili in the uropathogenic Echerichia coli, essential to the bacterial pathogenicity, is a complex molecular process, which involves several protein components of the Pap gene cluster. A crucial role in the process is played by the chaperone PapD and by the PapE pilus subunit. Interestingly, PapE exhibits an Ig-like fold with a missing strand. The missing G strand is donated by the chaperone during pilin folding and by adjacent pilus subunits in the final fibre. In order to obtain a detailed picture at atomic level of the molecular events related to this process, we undertook molecular dynamics studies of the non-canonical immuno-globulin-like PapE in its unliganded state. These analyses were extended to the complexes of PapE with the complementary G(1) strand of PapD and with the N-terminal extension of PapK. All three systems investigated were stable in the time interval considered (20 ns). However, significant differences in their local and overall flexibilities were detected. Notably, the equilibrated structure of unliganded PapE, which is difficult to characterise experimentally, displays unexpected features. Indeed, a significant rearrangement of the local structure of the groove, which hosts the complementary strands, is observed. This reorganisation, characterised by the formation of several new hydrogen bonds, leads to a closure of the groove that likely makes pilin polymerisation more difficult. These data suggest that chaperone release and pilin-pilin association must be concerted processes and that chaperone plays an important role in preventing pilin transitions towards states that are not prone to polymerise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / physiology
  • Escherichia coli / chemistry
  • Escherichia coli / growth & development*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Escherichia coli Proteins / physiology
  • Fimbriae Proteins / chemistry
  • Fimbriae Proteins / metabolism
  • Fimbriae Proteins / physiology
  • Fimbriae, Bacterial / chemistry*
  • Fimbriae, Bacterial / physiology
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Models, Molecular*
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / metabolism
  • Molecular Chaperones / physiology
  • Morphogenesis*
  • Periplasmic Proteins / chemistry
  • Periplasmic Proteins / metabolism
  • Periplasmic Proteins / physiology
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Proton-Translocating ATPases / chemistry
  • Proton-Translocating ATPases / metabolism
  • Proton-Translocating ATPases / physiology

Substances

  • Bacterial Proteins
  • Escherichia coli Proteins
  • Membrane Proteins
  • Molecular Chaperones
  • PapD protein, E coli
  • PapK protein, bacteria
  • Periplasmic Proteins
  • Protein Subunits
  • Fimbriae Proteins
  • Proton-Translocating ATPases
  • AtpH protein, E coli