The Cullin-RING ligases (CRLs) are the largest family of ubiquitin E3s activated by neddylation and regulated by the deneddylase COP9 signalosome (CSN). The inositol polyphosphate metabolites promote the formation of CRL–CSN complexes, but with unclear mechanism of action. Here, we provide structural and genetic evidence supporting inositol hexakisphosphate (IP6) as a general CSN cofactor recruiting CRLs. We determined the crystal structure of IP6 in complex with CSN subunit 2 (CSN2), based on which we identified the IP6-corresponding electron density in the cryoelectron microscopy map of a CRL4A–CSN complex. IP6 binds to a cognate pocket formed by conserved lysine residues from CSN2 and Rbx1/Roc1, thereby strengthening CRL–CSN interactions to dislodge the E2 CDC34/UBE2R from CRL and to promote CRL deneddylation. IP6 binding-deficient Csn2K70E/K70E knockin mice are embryonic lethal. The same mutation disabled Schizosaccharomyces pombe Csn2 from rescuing UV-hypersensitivity of csn2-null yeast. These data suggest that CRL transition from the E2-bound active state to the CSN-bound sequestered state is critically assisted by an interfacial IP6 small molecule, whose metabolism may be coupled to CRL–CSN complex dynamics.

Aim The genus Xylocarpus contains two mangrove species, X. granatum and X. moluccensis, and a rare non‐mangrove, X. rumphii. The two mangrove species are ideal models to study the biogeography of coastal plants with a unique dispersal ability, that is via buoyant propagules. We constructed the phylogeny of Xylocarpus and its relatives and determined the population structures of the two mangrove species. We aimed to elucidate the roles of continental drift and long‐distance dispersal (LDD) in shaping the present‐day distribution of Xylocarpus and to determine the factors affecting the patterns of population differentiation. Location The Indo‐West Pacific (IWP) region. Methods Thirty populations of X. granatum, 15 of X. moluccensis and four of X. rumphii were sampled across the IWP region. Five chloroplast DNA intergenic spacers were sequenced for Xylocarpus and outgroup species to determine divergence times. The genetic diversity, divergence and structure of the two mangrove species were further analysed using five nuclear and two chloroplast DNA loci. Migrations between oceanic regions were estimated. Results The genus Xylocarpus diverged from its sister genus Carapa approximately 19.4 Ma. The populations of X. granatum differentiated into three groups, with genetic breaks present across the Malay Peninsula and Wallacea, whereas X. moluccensis populations differentiated into two groups, with a genetic break present only across the Malay Peninsula. Migration was also observed between populations of the Southeast Asian and Australasian regions in X. moluccensis but not in X. granatum. Main conclusion Since Xylocarpus originated after the breakup of Gondwana and subsequent plate motions, its current distribution range should have been facilitated by present‐day LDD instead of past continental drift. Despite the capacity of LDD, the presence of differing population structures across land barriers (the Sunda and Sahul Shelves) and ocean currents indicated differential limitations in the dispersal capabilities of X. granatum and X. moluccensis.

Sodium polystyrene sulfonate (SPS), FDA-approved more than 60 years ago for treating hyperkalemia, is an ion exchange resin that works by exchanging sodium for potassium in the colon. Though widely used in clinical practice, SPS use is not supported by well-designed clinical trials. In 2009, the FDA issued a warning that SPS was associated with colonic necrosis and other serious gastrointestinal adverse reactions. This article reviews the pros and cons of SPS therapy.

Myo-inositol tris/tetrakisphosphate kinases (ITPKs) catalyze diverse phosphotransfer reactions with myo-inositol phosphate and myo-inositol pyrophosphate substrates. However, the lack of structures of nucleotide-coordinated plant ITPKs thwarts a rational understanding of phosphotransfer reactions of the family. Arabidopsis possesses a family of four ITPKs of which two isoforms, ITPK1 and ITPK4, control inositol hexakisphosphate and inositol pyrophosphate levels directly or by provision of precursors. Here, we describe the specificity of Arabidopsis ITPK4 to pairs of enantiomers of diverse inositol polyphosphates and show how substrate specificity differs from Arabidopsis ITPK1. Moreover, we provide a description of the crystal structure of ATP-coordinated AtITPK4 at 2.11 Å resolution that along with description of the enantiospecificity of the enzyme affords a molecular explanation for the diverse phosphotransferase activity of this enzyme. That Arabidopsis ITPK4 has a Km for ATP in the tens of micromolar range, potentially explains how, despite the large-scale abolition of InsP6, InsP7 and InsP8 synthesis in Atitpk4 mutants, Atitpk4 lacks the phosphate starvation responses of Atitpk1 mutants. We further demonstrate that Arabidopsis ITPK4 and its homologs in other plants possess an N-terminal haloacid dehalogenase-like fold not previously described. The structural and enzymological information revealed will guide elucidation of ITPK4 function in diverse physiological contexts, including InsP8-dependent aspects of plant biology.