Fig. 7: Pore formation of membrane-inserted mGSDMA3Nterm oligomers.
From: Gasdermin-A3 pore formation propagates along variable pathways
a Pore formation of an arc-shaped oligomer assembled from 16 mGSDMA3Nterm (n = 8/8 simulations). b Lipid withdrawal from mGSDMA3Nterm forming the arc-shaped oligomer shown in (a) at higher time resolution and structural detail. The hydrophilic (polar) surface of the transmembrane β-sheet formed by adjacent mGSDMA3Nterm causes water to penetrate into the membrane. The intrusion of water along the β-sheet is followed by the reassembly of lipid headgroups (yellow), whose withdrawal from the hydrophilic surface opens the transmembrane pore. c Pore formation of a slit-shaped oligomer assembled from 14 mGSDMA3Nterm. The lipids of the pre-pore fuse into the surrounding membrane (observed in 1 of 5, n = 1/5 simulations). d Pore formation of a ring-shaped oligomer assembled from 30 mGSDMA3Nterm. Lipids left ring-shaped oligomers assembled from 27 (n = 7/7 simulations) or 30 (n = 6/6 simulations) mGSDMA3Nterm as vesicles. mGSDMA3Nterm are colored in purple, lipid fatty acid chains light gray, and lipid headgroups dark gray. Lipids withdrawing from the transmembrane β-sheet thereby forming the transmembrane pore are colored green with yellow headgroups. The top row in each subfigure shows the cytoplasmic view, the bottom row the side view. Simulation times are indicated for each snapshot. Scale bars, 10 nm. The entire simulations are shown in Supplementary Movie 2–10. Additional coarse-grained MD simulations of arc-, slit- and ring-shaped oligomers forming transmembrane pores are shown in Supplementary Fig. 15.
