Editors' ChoiceBiochemistry

Inflammasomes take the wheel

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Sci. Signal.  27 Oct 2015:
Vol. 8, Issue 400, pp. ec314
DOI: 10.1126/scisignal.aad7044

Cells require microbial ligand binding to sense pathogens (see the Perspective by Liu and Xiao). Binding to the family of NOD-like receptors triggers the assembly of large protein signaling complexes called inflammasomes, leading infected cells to die and produce inflammatory mediators. Hu et al. and Zhang et al. use cryo–electron microscopy to uncover the structural and biochemical basis of two such receptors: NAIP2, which directly binds microbial ligands, and NLRC4, a protein functioning directly downstream. A self-propagating activation mechanism of downstream inflammasome signaling starts with one molecule of NAIP4 directly binding its microbial ligand. NAIP4 then catalyzes the activation of 10 to 12 NLRC4 molecules to form a wheel-like structure.

Z. Hu, Q. Zhou, C. Zhang, S. Fan, W. Cheng, Y. Zhao, F. Shao, H.-W. Wang, S.-F. Sui, J. Chai, Structural and biochemical basis for induced self-propagation of NLRC4. Science 350, 399–404 (2015). [Abstract] [Full Text]

L. Zhang, S. Chen, J. Ruan, J. Wu, A. B. Tong, Q. Yin, Y. Li, L. David, A. Lu, W. L. Wang, C. Marks, Q. Ouyang, X. Zhang, Y. Mao, H. Wu, Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization. Science 350, 404–409 (2015). [Abstract] [Full Text]

Z. Liu, T. S. Xiao, Assembling the wheel of death. Science 350, 376–377 (2015). [Abstract] [Full Text]