Molecular dynamics studies of the P pilus rod subunit PapA

J Pept Sci. 2009 Mar;15(3):192-9. doi: 10.1002/psc.1084.

Abstract

Adhesion of uropathogenic Escherichia coli to host tissues is mediated by pili, which extend from the outer cell membrane of the bacterium. Here we report molecular dynamics (MD) characterizations of the major constituent of P pili from the uropathogenic E. coli, PapA, in unliganded state and in complex with the G1 strand of the chaperone PapD. To mimic the PapA response to the gradual dissociation of the PapD G1 strand and to evaluate the role of PapA chaperone recognition sites, we also carried out MD simulations of complexes of PapA with fragments of PapD G1 strand, that leave either the P4 or both P3 and P4 sites unoccupied. Data on the unbound form of PapA indicate that, upon release of the chaperone, PapA evolves toward compact states that are likely not prone to subunit-subunit association. In line with recent experimental reports, this finding implies that chaperone release and subunit-subunit association must be concerted. Our data also indicated that the gradual unbinding of the chaperone from the PapA groove has increasingly strong structural consequences. Indeed, the release of the chaperone from the site P4, which is closest to the initiation site (P5), does not have dramatic effects on the domain structure, whereas its release from both the P4 and the adjacent P3 sites induces a quick structural transition toward a collapsed state, where the subunit groove is obstructed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation*
  • Escherichia coli Proteins / chemistry*
  • Fimbriae Proteins / chemistry*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Thermodynamics

Substances

  • AtpA protein, E coli
  • Escherichia coli Proteins
  • Fimbriae Proteins