NAD depletion as pathogen response: One way that plants respond to pathogen infection is by sacrificing the infected cells. The nucleotide-binding leucine-rich repeat immune receptors responsible for this hypersensitive response carry Toll/interleukin-1 receptor (TIR) domains. In two papers, Horsefield et al. and Wan et al. report that these TIR domains cleave the metabolic cofactor nicotinamide adenine dinucleotide (NAD ⁺ ) as part of their cell-death signaling in response to pathogens. Similar signaling links mammalian TIR-containing proteins to NAD ⁺ depletion during Wallerian degeneration of neurons. Science , this issue p. 793 , p. 799

Universal Immune Function: Certain pathogen effectors are detected in plants by cytoplasmic receptors. First solving the crystal structures of Arabidopsis receptors, Williams et al. (p. 299 ; see the Perspective by Nishimura and Dangl ) discovered that in the resting state, the structures form a heterodimer that readies the complex for effector binding and keeps the signaling domains from firing too early. Once the pathogen effector binds, the structure of the complex shifts such that the signaling domains can form a homodimer to initiate downstream signaling. Similarities between these plant-pathogen receptors and Toll-like receptors in animals suggest the molecular mechanisms may translate broadly.

The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a β-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.