Abstract
Pore-forming proteins (PFPs) are a broad class of molecules that comprise various families, structural folds, and assembly pathways. In nature, PFPs are most often deployed by their host organisms to defend against other organisms. In humans, this is apparent in the immune system, where several immune effectors possess pore-forming activity. Furthermore, applications of PFPs are found in next-generation low-cost DNA sequencing, agricultural crop protection, pest control, and biosensing. The advent of cryoEM has propelled the field forward. Nevertheless, significant challenges and knowledge-gaps remain. Overcoming these challenges is particularly important for the development of custom, purpose-engineered PFPs with novel or desired properties. Emerging single-molecule techniques and methods are helping to address these unanswered questions. Here we review the current challenges, problems, and approaches to studying PFPs.
Highlights
Pore-forming proteins (PFPs) represent a highly diverse and growing class of molecules identified in all kingdoms of life (Figure 1)
PFPs are remarkable in that they transition from a soluble molecule into an integral transmembrane protein
These steps can occur in varying orders across the different PFP families (Figure 1b)
Summary
Pore-forming proteins (PFPs) represent a highly diverse and growing class of molecules identified in all kingdoms of life (Figure 1). Fundamental questions concerning PFP biology can be classified into key research themes, including structural intermediates, kinetics of pore formation, mode-of-action, PFP-lipid interactions, and translational applications in biotechnology and medicine Driving these investigations are a broad set of cutting-edge experimental and computational techniques (Figures 2, 3). By measuring the steps and transient drops in current, their duration and amplitude, various details of the underlying molecular process can be extracted This includes the size distribution of the nanopore, interactions with solutes or binding partners (e.g. Vip1/2), as well as pore assembly pathways and kinetics in the context of systems that form pores via a growing-arc mechanism (Figure 1b) [113,114,115,116,117]. De novo design of simple α and β transmembrane channels was recently achieved [159,160], potentially laying the foundation for tailor-made PFPs designed for specific analytes and applications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
