6LG3

Crystal structure of a bacterial toxin from Mycobacterium tuberculosis

Summary for 6LG3

• Entry DOI: 10.2210/pdb6lg3/pdb
• Descriptor: PhiRv1 phage protein (2 entities in total)
• Functional Keywords: bacterial toxin, toxin
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 8038.86

Authors

Zhou, J.,Jiang, Y.,Luo, Z.,Yin, L. (deposition date: 2019-12-04, release date: 2020-11-04, Last modification date: 2023-11-22)

Primary citation

Qu, Z.,Zhou, J.,Zhou, Y.,Xie, Y.,Jiang, Y.,Wu, J.,Luo, Z.,Liu, G.,Yin, L.,Zhang, X.L.
Mycobacterial EST12 activates a RACK1-NLRP3-gasdermin D pyroptosis-IL-1 beta immune pathway.
Sci Adv, 6:-, 2020

PubMed Abstract: Pyroptosis, an inflammatory form of programmed cell death, has been implicated in eliminating pathogenic infections. However, macrophage pyroptosis-related proteins from () have largely gone unexplored. Here, we identified a cell pyroptosis-inducing protein, Rv1579c, named EST12, secreted from the H37Rv region of difference 3. EST12 binds to the receptor for activated C kinase 1 (RACK1) in macrophages, and the EST12-RACK1 complex recruits the deubiquitinase UCHL5 to promote the K48-linked deubiquitination of NLRP3, subsequently leading to an NLRP3 inflammasome caspase-1/11-pyroptosis gasdermin D-interleukin-1β immune process. Analysis of the crystal structure of EST12 reveals that the amino acid Y80 acts as a critical binding site for RACK1. An EST12-deficient strain (H37RvΔEST12) displayed higher susceptibility to infection in vitro and in vivo. These results provide the first proof that RACK1 acts as an endogenous host sensor for pathogens and that EST12-RACK1-induced pyroptosis plays a pivotal role in -induced immunity.

PubMed: 33097533
DOI: 10.1126/sciadv.aba4733

Experimental method

X-RAY DIFFRACTION (1.90057258182 Å)