Cleavage-independent activation of ancient eukaryotic gasdermins and structural mechanisms.

Autor: Li Y; Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 101408, China., Hou Y; Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Sun Q; Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; National Institute of Biological Sciences, Beijing, Beijing 102206, China., Zeng H; Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; National Institute of Biological Sciences, Beijing, Beijing 102206, China., Meng F; Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 101408, China., Tian X; MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing 100193, China., He Q; MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing 100193, China., Shao F; Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; National Institute of Biological Sciences, Beijing, Beijing 102206, China.; Research Unit of Pyroptosis and Immunity, Chinese Academy of Medical Sciences and National Institute of Biological Sciences, Beijing 102206, China.; Changping Laboratory, Beijing 102206, China.; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, China.; New Cornerstone Science Laboratory, Shenzhen 518054, China., Ding J; Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 101408, China.; National Institute of Biological Sciences, Beijing, Beijing 102206, China.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 May 17; Vol. 384 (6697), pp. adm9190. Date of Electronic Publication: 2024 May 17.
DOI: 10.1126/science.adm9190
Abstrakt: Gasdermins (GSDMs) are pore-forming proteins that execute pyroptosis for immune defense. GSDMs are two-domain proteins activated by proteolytic removal of the inhibitory domain. In this work, we report two types of cleavage-independent GSDM activation. First, Tricho GSDM, a pore-forming domain-only protein from the basal metazoan Trichoplax adhaerens , is a disulfides-linked autoinhibited dimer activated by reduction of the disulfides. The cryo-electron microscopy (cryo-EM) structure illustrates the assembly mechanism for the 44-mer Tricho GSDM pore. Second, RCD-1-1 and RCD-1-2, encoded by the polymorphic regulator of cell death-1 ( rcd-1 ) gene in filamentous fungus Neurospora crassa , are also pore-forming domain-only GSDMs. RCD-1-1 and RCD-1-2, when encountering each other, form pores and cause pyroptosis, underlying allorecognition in Neurospora . The cryo-EM structure reveals a pore of 11 RCD-1-1/RCD-1-2 heterodimers and a heterodimerization-triggered pore assembly mechanism. This study shows mechanistic diversities in GSDM activation and indicates versatile functions of GSDMs.
Databáze: MEDLINE
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