Gram-negative bacteria deploy several routes to move proteins across their outer membrane. Among them, the type V (autotransporter) pathway is often considered the simplest, yet key steps in protein export remain unresolved. EspP, a type Va autotransporter from Escherichia coli , secretes an extracellular serine protease that contributes to virulence, but the mechanism of passenger translocation is still unclear. Here, we construct a multiscale model that couples a shape-based coarse-grained (SBCG) model representing the EspP-BamA hybrid barrel channel and outer membrane environment with a residue-based coarse-grained model of the passenger domain. Based on the SBCG tools in VMD, we introduce an all-atom trajectory-informed scoring factor to evaluate the topological stability of the SBCG graph and update bead connectivity based on the dynamics. The SBCG channel is modeled in outer-membrane environments with diverse lipid compositions, while the residue-based passenger captures sequence-dependent behavior in each environment. Together, this integrated framework enables simulations of EspP secretion at more realistic timescales and supports hypothesis testing on how membrane composition, electrostatic environment, and passenger sequence jointly regulate type V autotransport.
Yang et al. (Sun,) studied this question.