Immunological properties of oxygen-transport proteins: hemoglobin,hemocyanin and hemerythrin

It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon is the oxygen-transport protein hemoglobin. Aside from respiration, hemoglobin and hemoglobin-derived peptides have been associated with immune modulation, hematopoiesis, signal transduction and microbicidal activities in metazoans. Likewise, the functional equivalents to hemoglobin in invertebrates, namely hemocyanin and hemerythrin, act as potent immune effectors under certain physiological conditions. The purpose of this review is to evaluate the true extent of oxygen-transport protein dynamics in innate immunity, and to impress upon the reader the multi-functionality of these ancient proteins on the basis of their structures. In this context, erythrocyte–pathogen antibiosis and the immune competences of various erythroid cells are compared across diverse taxa.     

Human CtIP promotes DNA end resection

In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of replication protein A (RPA) and the protein kinase ATR to DSBs, and for the ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient homologous recombination. Finally, we reveal that CtIP has sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.     

Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis

With more than 55,000 members identified so far in all forms of life, the family of terpene or terpenoid natural products represents the epitome of molecular biodiversity. A well-known and important member of this family is the polycyclic diterpenoid Taxol (paclitaxel), which promotes tubulin polymerization and shows remarkable efficacy in cancer chemotherapy. The first committed step of Taxol biosynthesis in the Pacific yew (Taxus brevifolia) is the cyclization of the linear isoprenoid substrate geranylgeranyl diphosphate (GGPP) to form taxa-4(5),11(12)diene, which is catalysed by taxadiene synthase. The full-length form of this diterpene cyclase contains 862 residues, but a roughly 80-residue amino-terminal transit sequence is cleaved on maturation in plastids. We now report the X-ray crystal structure of a truncation variant lacking the transit sequence and an additional 27 residues at the N terminus, hereafter designated TXS. Specifically, we have determined structures of TXS complexed with 13-aza-13,14-dihydrocopalyl diphosphate (1.82?? resolution) and 2-fluorogeranylgeranyl diphosphate (2.25?? resolution). The TXS structure reveals a modular assembly of three α-helical domains. The carboxy-terminal catalytic domain is a class?I terpenoid cyclase, which binds and activates substrate GGPP with a three-metal ion cluster. The N-terminal domain and a third 'insertion' domain together adopt the fold of a vestigial class?II terpenoid cyclase. A class?II cyclase activates the isoprenoid substrate by protonation instead of ionization, and the TXS structure reveals a definitive connection between the two distinct cyclase classes in the evolution of terpenoid biosynthesis.     

Antagonistic pathways in neurons exposed to body fluid regulate social feeding in Caenorhabditis elegans

Wild isolates of Caenorhabditis elegans can feed either alone or in groups. This natural variation in behaviour is associated with a single residue difference in NPR-1, a predicted G-protein-coupled neuropeptide receptor related to Neuropeptide Y receptors. Here we show that the NPR-1 isoform associated with solitary feeding acts in neurons exposed to the body fluid to inhibit social feeding. Furthermore, suppressing the activity of these neurons, called AQR, PQR and URX, using an activated K(+) channel, inhibits social feeding. NPR-1 activity in AQR, PQR and URX neurons seems to suppress social feeding by antagonizing signalling through a cyclic GMP-gated ion channel encoded by tax-2 and tax-4. We show that mutations in tax-2 or tax-4 disrupt social feeding, and that tax-4 is required in several neurons for social feeding, including one or more of AQR, PQR and URX. The AQR, PQR and URX neurons are unusual in C. elegans because they are directly exposed to the pseudocoelomic body fluid. Our data suggest a model in which these neurons integrate antagonistic signals to control the choice between social and solitary feeding behaviour.     

The most primitive osteichthyan braincase?

Most living vertebrates, from teleosts to tetrapods, are osteichthyans (bony fishes), but the origin of this major group is poorly understood. The actinopterygians (ray-finned bony fishes) are the most successful living vertebrates in terms of diversity. They appear in the fossil record in the Late Silurian but are poorly known before the Late Devonian. Here we report the discovery of the oldest and most primitive actinopterygian-like osteichthyan braincase known, from 400-million-year-old limestone in southeastern Australia. This specimen displays previously unknown primitive conditions, in particular, an opening for a cartilaginous eyestalk. It provides an important and unique counterpart to the similarly aged and recently described Psarolepis from China and Vietnam. The contrasting features of these specimens, and the unusual anatomy of the new specimen in particular, provide new insights into anatomical conditions close to the evolutionary radiation of all modern osteichthyan groups.     

Conformational studies ofcis-10-methyl-2-decalones

Zusammenfassung Im Kernresonanzspektrum einiger substituiertercis-2-Decalone wurden die chemischen Verschiebungen angulärer Methylgruppen untersucht. Dabei wurde festgestellt, dass die Verbindungen vorwiegend in der nicht-steroidalen Sessel-Sessel-Konformation vorliegen. Das Vorzeichen der ORD Cotton-Kurven dieser Ketone muss durch das untergeordnete Vorhandensein einer Konformation sehr starker Amplitude, wie z. B. der Twist-Form, bedingt sein.     

Advanced optics in a jellyfish eye

Cubozoans, or box jellyfish, differ from all other cnidarians by an active fish-like behaviour and an elaborate sensory apparatus. Each of the four sides of the animal carries a conspicuous sensory club (the rhopalium), which has evolved into a bizarre cluster of different eyes. Two of the eyes on each rhopalium have long been known to resemble eyes of higher animals, but the function and performance of these eyes have remained unknown. Here we show that box-jellyfish lenses contain a finely tuned refractive index gradient producing nearly aberration-free imaging. This demonstrates that even simple animals have been able to evolve the sophisticated visual optics previously known only from a few advanced bilaterian phyla. However, the position of the retina does not coincide with the sharp image, leading to very wide and complex receptive fields in individual photoreceptors. We argue that this may be useful in eyes serving a single visual task. The findings indicate that tailoring of complex receptive fields might have been one of the original driving forces in the evolution of animal lenses.