One of the main mechanisms by which bacteria and archaea interact with their environment is through the use of long protein filaments called Type IV pili (T4P). T4P are comprised of thousands of copies of a protein called pilin and can be micrometers in length. Individual pilin subunits are “ladle-shaped”, consisting of a globular C-terminal domain and a helical N-terminal domain. These filaments can act as “grappling hooks”, allowing microorganisms to attach to other cells and move along surfaces, while also supporting against extremely large tension forces. The structure of the T4P from <i>Neisseria meningitidis </i>(Nm T4P) was recently solved experimentally (Kolappan, et al. , Nat. Commun. 7, 2016) and represents the highest resolution model of a T4P filament to date. Interestingly, in the structural Nm T4P model, a region of the helical N-terminal domain of the pilin subunits was “melted”, in contrast to the entirely helical structure observed in an earlier model of the T4P from <i>Neisseria gonorrhoeae. </i>Here the Nm T4P structural model is investigated using a combined all-atom molecular dynamics and coarse-grained analysis approach. Specifically, simulations of a Nm T4P filament consisting of 18 pilin subunits is simulated in explicit solvent using the GPU implementation of pmemd in Amber16. It was observed that over several hundred nanoseconds of simulation the “melted” region of pilin alpha helices could adopt transient secondary structure, however predominately remained unstructured as observed in the initial model. Furthermore, the filament model remained structurally stable as gauged by backbone root mean squared deviation, with individual pilin subunits within the filament also demonstrating a high degree of structural stability. Stable interactions between pilin subunits were determined from the simulations, indicating that the alpha helical regions of pilin subunits pack tightly in the filament core, and that the pilin globular C-terminal domains exhibit a comparatively smaller number of interactions along the filament surface. A coarse-grained analysis of the T4P filament allowed for the calculation of the T4P filament persistence length and the distribution of pilin subunit twist angles along the filament axis, demonstrating a degree of structural heterogeneity within the filament.

All-atom simulation and coarse-grained analysis of the type IV pilus filament from Neisseria meningitidis

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.