Preprint Article Version 1 This version is not peer-reviewed

Steric Blockage of Lysenin Toxin by Crowding

Version 1 : Received: 2 May 2020 / Approved: 5 May 2020 / Online: 5 May 2020 (16:18:48 CEST)

How to cite: Munguira, I.L.; Barbas, A. Steric Blockage of Lysenin Toxin by Crowding. Preprints 2020, 2020050088 (doi: 10.20944/preprints202005.0088.v1). Munguira, I.L.; Barbas, A. Steric Blockage of Lysenin Toxin by Crowding. Preprints 2020, 2020050088 (doi: 10.20944/preprints202005.0088.v1).

Abstract

Increasing evidence signals the importance of macromolecular crowding on the regulation of the membrane protein activity. Lysenin is a pore forming toxin that forms crowded assemblies in membrane containing sphingomyelin microdomains. We studied the role of crowding on the activity of Lysenin thanks to High Speed Atomic Force Microscopy. In this study we show that pore formation requires available space around to take place, being sterically block in crowded environments, and verified it with nonSupported Lipid Bilayers mimicking the mechanical conditions of cell membranes. A continuous pH decrease and a single molecule compression experiments show that pore formation liberates membrane space leading to prepore-to-pore transitions. The study of the effects of prepore insertion comparing pore formation induced by sudden pH decrease in lysenin assemblies with thousand simulations show that liberation of space unblocks pore formation and could contribute to elude the cellular non-immune defences. Based on our findings we propose a refinement of current prepore structure and insertion models. We envision novel antibiotic strategies based on toxin-bindingdomains “crowders”.

Subject Areas

Pore Forming Toxins; crowding; prepore-to-pore transition

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