Structure of the Neisserial outer membrane protein Opa₆₀: loop flexibility essential to receptor recognition and bacterial engulfment

J Am Chem Soc. 2014 Jul 16;136(28):9938-46. doi: 10.1021/ja503093y. Epub 2014 May 19.

Abstract

The structure and dynamics of Opa proteins, which we report herein, are responsible for the receptor-mediated engulfment of Neisseria gonorrheae or Neisseria meningitidis by human cells and can offer deep understanding into the molecular recognition of pathogen-host receptor interactions. Such interactions are vital to understanding bacterial pathogenesis as well as the mechanism of foreign body entry to a human cell, which may provide insights for the development of targeted pharmaceutical delivery systems. The size and dynamics of the extracellular loops of Opa60 required a hybrid refinement approach wherein membrane and distance restraints were used to generate an initial NMR structural ensemble, which was then further refined using molecular dynamics in a DMPC bilayer. The resulting ensemble revealed that the extracellular loops, which bind host receptors, occupy compact conformations, interact with each other weakly, and are dynamic on the nanosecond time scale. We predict that this conformational sampling is critical for enabling diverse Opa loop sequences to engage a common set of receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry*
  • Dimyristoylphosphatidylcholine
  • Extracellular Space / chemistry
  • Foreign-Body Reaction
  • Host-Pathogen Interactions
  • Humans
  • Lipid Bilayers
  • Molecular Conformation
  • Nanotechnology
  • Neisseria gonorrhoeae / chemistry*
  • Neisseria meningitidis / chemistry*

Substances

  • Bacterial Outer Membrane Proteins
  • Lipid Bilayers
  • Dimyristoylphosphatidylcholine