This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Nematocytes, the stinging cells of cnidarians, are the most evolutionarily ancient venom apparatus. These nanosyringe-like weaponry systems reach pressures of approximately 150 atmospheres before discharging and punching through the outer layer of the prey or predator at accelerations of more than 5 million g, making them one of the fastest biomechanical events known. To gain better understanding of the function of the complex, phylum-specific nematocyst organelle, and its venom payload, we compared the soluble nematocyst's proteome from the sea anemone Anemonia viridis, the jellyfish Aurelia aurita, and the hydrozoan Hydra magnipapillata, each belonging to one of the three basal cnidarian lineages which diverged over 600 Ma. Although the basic morphological and functional characteristics of the nematocysts of the three organisms are similar, out of hundreds of proteins identified in each organism, only six are shared. These include structural proteins, a chaperone which may help maintain venon activity over extended periods, and dickkopf, an enigmatic Wnt ligand which may also serve as a toxin. Nevertheless, many protein domains are shared between the three organisms' nematocyst content suggesting common proteome functionalities. The venoms of Hydra and Aurelia appear to be functionally similar and composed mainly of cytotoxins and enzymes, whereas the venom of the Anemonia is markedly unique and based on peptide neurotoxins. Cnidarian venoms show evidence for functional recruitment, yet evidence for diversification through positive selection, common to other venoms, is lacking. The final injected nematocyst payload comprises a mixture of dynamically evolving proteins involved in the development, maturation, maintenance, and discharge of the nematocysts, which is unique to each organism and potentially to each nematocyst type.

No abstract

Summary The respiratory and intestinal tracts are exposed to physical and biological hazards accompanying the intake of air and food. Likewise, the vasculature is threatened by inflammation and trauma. Mucin glycoproteins and the related von Willebrand factor guard the vulnerable cell layers in these diverse systems. Colon mucins additionally house and feed the gut microbiome. Here, we present an integrated structural analysis of the intestinal mucin MUC2. Our findings reveal the shared mechanism by which complex macromolecules responsible for blood clotting, mucociliary clearance, and the intestinal mucosal barrier form protective polymers and hydrogels. Specifically, cryo-electron microscopy and crystal structures show how disulfide-rich bridges and pH-tunable interfaces control successive assembly steps in the endoplasmic reticulum and Golgi apparatus. Remarkably, a densely O-glycosylated mucin domain performs an organizational role in MUC2. The mucin assembly mechanism and its adaptation for hemostasis provide the foundation for rational manipulation of barrier function and coagulation.