Mari, Stefania A.Show all
- Journal Article
Rights / licenseCreative Commons Attribution 4.0 International
Gasdermin‐D (GSDMD), a member of the gasdermin protein family, mediates pyroptosis in human and murine cells. Cleaved by inflammatory caspases, GSDMD inserts its N‐terminal domain (GSDMDNterm) into cellular membranes and assembles large oligomeric complexes permeabilizing the membrane. So far, the mechanisms of GSDMDNterm insertion, oligomerization, and pore formation are poorly understood. Here, we apply high‐resolution (≤ 2 nm) atomic force microscopy (AFM) to describe how GSDMDNterm inserts and assembles in membranes. We observe GSDMDNterm inserting into a variety of lipid compositions, among which phosphatidylinositide (PI(4,5)P2) increases and cholesterol reduces insertion. Once inserted, GSDMDNterm assembles arc‐, slit‐, and ring‐shaped oligomers, each of which being able to form transmembrane pores. This assembly and pore formation process is independent on whether GSDMD has been cleaved by caspase‐1, caspase‐4, or caspase‐5. Using time‐lapse AFM, we monitor how GSDMDNterm assembles into arc‐shaped oligomers that can transform into larger slit‐shaped and finally into stable ring‐shaped oligomers. Our observations translate into a mechanistic model of GSDMDNterm transmembrane pore assembly, which is likely shared within the gasdermin protein family. Show more
Journal / seriesEMBO Journal
Pages / Article No.
Subjectcell death; inflammation; gasdermin-D pore assembly; time-lapse high-resolution atomic force microscopy; transmission electron microscopy
Organisational unit02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.
03870 - Müller, Daniel J. / Müller, Daniel J.
160199 - Gleichzeitiges hochauflösendes Abbilden von Membranproteinen und dreidimensionales Kartieren der Wechselwirkungskräfte und Energielandschaften mit Liganden (SNF)
MoreShow all metadata