Uncovering the folding mechanism of pertactin: A comparative study of isolated and vectorial folding

In this study, we used molecular dynamics simulations and enhanced sampling methods to investigate the stability and folding of the passenger domain of pertactin, an autotransporter from Bordetella pertussis. Specifically, we employed steered molecular dynamics to simulate the unfolding of the entire passenger domain as well as self-learning adaptive umbrella sampling to compare the energetics of folding rungs of the β-helix independently ("isolated folding") versus folding rungs on top of a previously folded rung ("vectorial folding"). Our results showed that vectorial folding is highly favorable as compared to isolated folding; moreover, our simulations showed the C-terminal rung of the β-helix is the most resistant to unfolding, in agreement with previous studies that found the C-terminal half of the passenger domain to be more stable than the N-terminal one. Overall, this study provides new insights into the folding process of an autotransporter passenger domain and its potential role in secretion across the OM.PMID:36960532 | DOI:10.1016/j.bpj.2023.03.021
Source: Biophysical Journal - Category: Physics Authors: Source Type: research