Membrane stability is key for survival of a cell. I will describe recent breakthroughs in two areas of structural biology that circulate around the integrity of the cellular membrane. The eukaryotic cell controls its survival and its death by a tightly controlled protein system that responds to external and internal danger signals. The protein NINJ1 (Nerve injury induced protein 1) has recently emerged as the executor of membrane rupture in multiple cell death pathways [1]. I will describe the integrated structural biology approach that has resolved structure and mechanism of NINJ1-mediated plasma membrane rupture in pyroptosis [2] and discuss possible mechanisms of activation and execution, including the “cookie cutter”, the “mega-pore” and the “zipper” mechanism [2, 3].
In contrast, the outer membrane of Gram-negative bacteria is a potential Achilles heel suitable for attack by novel antibiotics. The integrity of this prokaryotic membrane is essential for cell survival, however, it is located at the periphery and not well protected by some of the canonical bacterial defense mechanisms. I will describe how several recently discovered novel antibiotics – the Bamabactins – inhibit the outer membrane insertase BAM to block outer membrane protein biogenesis and eventually kill the prokaryotic cell [4]. The two cases of protein-mediated membrane rupture expose intrinsic strengths and weakness of the prokaryotic and eukaryotic cell membranes.
References:
[1] Kayagaki N, Kornfeld OS, Lee BL et al. Nature 591, 131–136 (2021).
[2] Degen M, Santos JC, Pluhackova K et al. Nature 618, 1065–1071 (2023).
[3] David L et al. Cell 187, 2224–2235 (2024).
[4] Kaur H, Jakob RP et al. Nature 593, 125–129 (2021).