Bacterial gasdermins reveal an ancient mechanism of cell death

被引:174
作者
Johnson, Alex G. [1 ,2 ]
Wein, Tanita [3 ]
Mayer, Megan L. [4 ]
Duncan-Lowey, Brianna [1 ,2 ]
Yirmiya, Erez [3 ]
Oppenheimer-Shaanan, Yaara [3 ]
Amitai, Gil [3 ]
Sorek, Rotem [3 ]
Kranzusch, Philip J. [1 ,2 ,5 ]
机构
[1] Harvard Med Sch, Dept Microbiol, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA
[3] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
[4] Harvard Med Sch, Harvard Ctr Cryoelectron Microscopy, Boston, MA 02115 USA
[5] Dana Farber Canc Inst, Parker Inst Canc Immunotherapy, Boston, MA 02115 USA
基金
欧洲研究理事会; 以色列科学基金会;
关键词
SEQUENCE ALIGNMENT; MODEL; PYROPTOSIS;
D O I
10.1126/science.abj8432
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Gasdermin proteins form large membrane pores in human cells that release immune cytokines and induce lytic cell death. Gasdermin pore formation is triggered by caspase-mediated cleavage during inflammasome signaling and is critical for defense against pathogens and cancer. We discovered gasdermin homologs encoded in bacteria that defended against phages and executed cell death. Structures of bacterial gasdermins revealed a conserved pore-forming domain that was stabilized in the inactive state with a buried lipid modification. Bacterial gasdermins were activated by dedicated caspase-like proteases that catalyzed site-specific cleavage and the removal of an inhibitory C-terminal peptide. Release of autoinhibition induced the assembly of large and heterogeneous pores that disrupted membrane integrity. Thus, pyroptosis is an ancient form of regulated cell death shared between bacteria and animals.
引用
收藏
页码:221 / +
页数:41
相关论文
共 48 条
[1]   PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].
Adams, Paul D. ;
Afonine, Pavel V. ;
Bunkoczi, Gabor ;
Chen, Vincent B. ;
Davis, Ian W. ;
Echols, Nathaniel ;
Headd, Jeffrey J. ;
Hung, Li-Wei ;
Kapral, Gary J. ;
Grosse-Kunstleve, Ralf W. ;
McCoy, Airlie J. ;
Moriarty, Nigel W. ;
Oeffner, Robert ;
Read, Randy J. ;
Richardson, David C. ;
Richardson, Jane S. ;
Terwilliger, Thomas C. ;
Zwart, Peter H. .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221
[2]   The gasdermins, a protein family executing cell death and inflammation [J].
Broz, Petr ;
Pelegrin, Pablo ;
Shao, Feng .
NATURE REVIEWS IMMUNOLOGY, 2020, 20 (03) :143-157
[3]   IMG/M v.5.0: an integrated data management and comparative analysis system for microbial genomes and microbiomes [J].
Chen, I-Min A. ;
Chu, Ken ;
Palaniappan, Krishna ;
Pillay, Manoj ;
Ratner, Anna ;
Huang, Jinghua ;
Huntemann, Marcel ;
Varghese, Neha ;
White, James R. ;
Seshadri, Rekha ;
Smirnova, Tatyana ;
Kirton, Edward ;
Jungbluth, Sean P. ;
Woyke, Tanja ;
Eloe-Fadrosh, Emiley A. ;
Ivanova, Natalia N. ;
Kyrpides, Nikos C. .
NUCLEIC ACIDS RESEARCH, 2019, 47 (D1) :D666-D677
[4]   MolProbity: all-atom structure validation for macromolecular crystallography [J].
Chen, Vincent B. ;
Arendall, W. Bryan, III ;
Headd, Jeffrey J. ;
Keedy, Daniel A. ;
Immormino, Robert M. ;
Kapral, Gary J. ;
Murray, Laura W. ;
Richardson, Jane S. ;
Richardson, David C. .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :12-21
[5]  
Clave C., 2021, Fungal gasdermin-like proteins are controlled by proteolytic cleavage, DOI [10.1101/2021.06.03.446900, DOI 10.1101/2021.06.03.446900]
[6]  
Clave C., 2021, BIORXIV
[7]   Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment [J].
Cox, Juergen ;
Neuhauser, Nadin ;
Michalski, Annette ;
Scheltema, Richard A. ;
Olsen, Jesper V. ;
Mann, Matthias .
JOURNAL OF PROTEOME RESEARCH, 2011, 10 (04) :1794-1805
[8]   Molecular characterization of a fungal gasdermin-like protein [J].
Daskalov, Asen ;
Mitchell, Patrick S. ;
Sandstrom, Andrew ;
Vance, Russell E. ;
Glass, N. Louise .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (31) :18600-18607
[9]   Pore-forming activity and structural autoinhibition of the gasdermin family [J].
Ding, Jingjin ;
Wang, Kun ;
Liu, Wang ;
She, Yang ;
Sun, Qi ;
Shi, Jianjin ;
Sun, Hanzi ;
Wang, Da-Cheng ;
Shao, Feng .
NATURE, 2016, 535 (7610) :111-+
[10]   Coot:: model-building tools for molecular graphics [J].
Emsley, P ;
Cowtan, K .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 :2126-2132