Academic Journal
Coarse-grained simulation studies of gasdermin self-assembly and pore formation.
| Τίτλος: | Coarse-grained simulation studies of gasdermin self-assembly and pore formation. |
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| Συγγραφείς: | Jiang X; 2020 X-Lab, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, P.R. China; Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, P.R. China., Farrell JD; Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, P.R. China; School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, P.R. China; Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, P.R. China. Electronic address: farrelljd@iphy.ac.cn., Jiao F; Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, P.R. China., Dobnikar J; Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, P.R. China; School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, P.R. China; Wenzhou Institute of the University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325011, P.R. China; Faculty for Mathematics and Physics, University of Ljubljana, Ljubljana, Slovenia. |
| Πηγή: | Biophysical journal [Biophys J] 2026 Oct 06; Vol. 125 (19), pp. 5482-5493. Date of Electronic Publication: 2026 Aug 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Cell Press Country of Publication: United States NLM ID: 0370626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1542-0086 (Electronic) Linking ISSN: 00063495 NLM ISO Abbreviation: Biophys J Subsets: MEDLINE |
| Imprint Name(s): | Publication: Cambridge, MA : Cell Press Original Publication: New York, Published by Rockefeller University Press [etc.] for the Biophysical Society. |
| Ιατρικοί όροι (MeSH): | Molecular Dynamics Simulation* , Protein Multimerization*, Kinetics ; Porosity ; Protein Conformation |
| Περίληψη: | Gasdermins (GSDMs) are pore-forming proteins that trigger pyroptosis, an inflammatory cell death process that plays a crucial role in immunity. Recent experiments and atomistic simulations have shed light on GSDM molecular structure and their conformational transitions when inserting into the membrane to form pores. However, the dynamics of pore assembly remain incompletely understood. In this work, we propose a minimal coarse-grained model of GSDM proteins and run extensive molecular dynamics simulations that bridge the gap between atomistic simulations on a single molecule level and biological length and time scales relevant for membrane pore assembly. We observe supramolecular structures similar to those reported in experiments: rings, slits, and arcs with significantly different pore cross-sections. By informing our model with experimental observations, we show that the dominant regulatory factors for the assembly of pores are closely related to the kinetics of monomer conformational transition from prepore to pore state. When the monomer insertion kinetics is slow (late insertion), protein interaction strength is the key quantity promoting the formation of circular pores (rings), which maximize the pore area and consequentially the transport across the pore. In the case of fast (early) insertion, the ring formation is generally suppressed; we observe a prevalence of slit-like pores that are sub-optimal for transport. Different from the late insertion scenario, the rings are here promoted by increasing the membrane coverage with proteins. Our findings provide a mechanistic basis for understanding and potentially modulating pyroptotic cell death in various physiological and disease contexts. (Copyright © 2026 Biophysical Society. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| Entry Date(s): | Date Created: 20260805 Date Completed: 20261006 Latest Revision: 20261006 |
| Update Code: | 20261007 |
| DOI: | 10.1016/j.bpj.2026.07.031 |
| PMID: | 42552735 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1542-0086 |
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| DOI: | 10.1016/j.bpj.2026.07.031 |