The tertiary structure of group II introns: implications for biological function and evolution

Group II introns are some of the largest ribozymes in nature, and they are a major source of information about RNA assembly and tertiary structural organization. These introns are of biological significance because they are self-splicing mobile elements that have migrated into diverse genomes and played a major role in the genomic organization and metabolism of most life forms. The tertiary structure of group II introns has been the subject of many phylogenetic, genetic, biochemical and biophysical investigations, all of which are consistent with the recent crystal structure of an intact group IIC intron from the alkaliphilic eubacterium Oceanobacillus iheyensis. The crystal structure reveals that catalytic intron domain V is enfolded within the other intronic domains through an elaborate network of diverse tertiary interactions. Within the folded core, DV adopts an activated conformation that readily binds catalytic metal ions and positions them in a manner appropriate for reaction with nucleic acid targets. The tertiary structure of the group II intron reveals new information on motifs for RNA architectural organization, mechanisms of group II intron catalysis, and the evolutionary relationships among RNA processing systems. Guided by the structure and the wealth of previous genetic and biochemical work, it is now possible to deduce the probable location of DVI and the site of additional domains that contribute to the function of the highly derived group IIB and IIA introns.     

A comparative study of the biological properties of some sea snake venoms.

1. The protease, phosphodiesterase, alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase, phospholipase A, 5'-nucleotidase, hyaluronidase, arginine ester hydrolase, procoagulant, anticoagulant and hemorrhagic activities of ten samples of venoms from seven taxa of sea snakes were examined. 2. The results show that venoms of sea snakes of both subfamilies of Hydrophiinae and Laticaudinae are characterized by a very low level of enzymatic activities, except phospholipase A activity and, for some species, hyaluronidase activity. 3. Because of the low levels of enzymatic activities and the total lack of procoagulant and hemorrhagic activities, venom biological properties are not useful for the differentiation of species of sea snakes. Nevertheless, the unusually low levels of enzymatic activities of sea snake venoms may be used to distinguish sea snake venoms from other elapid or viperid venoms.     

Reduction and S-nitrosation of the neuropeptide oxytocin: implications for its biological function.

Oxytocin (OT; Cys-Tyr-Ile-Gln-Asn-Cys-Pro-leu-Gly), a posterior pituitary peptide hormone, is characterized by a Cys1-Cys6 disulfide bond in its stable, isolated state. This paper describes a simple, one-step method for the production of OT in its reduced, dithiol form (OT dithiol), free of reducing agent. The effects of temperature, pH, and metal-ion chelators on the autoxidation of OT dithiol were examined to establish if this form is likely to persist under biological conditions. It was found that OT dithiol has a half-life of 1.8h with respect to reformation of OT disulfide at 37 degrees C and pH 6.9 in the presence of the copper chelators, DTPA and neocuproine. S-Nitrosation of OT dithiol by acidified nitrite at pH 3.0 was examined by absorption spectroscopy and HPLC-UV-MS, which revealed that both singly and doubly S-nitrosated OT are formed. These results suggest novel chemical aspects to OT signaling, the biological implications of which are discussed here.     

The receptor-binding sequence of urokinase. A biological function for the growth-factor module of proteases

Previous studies have shown that the region of human urokinase-type plasminogen activator (uPA) responsible for receptor binding resides in the amino-terminal fragment (ATF, residues 1-135) (Stoppelli, M.P., Corti, A., Soffientini, A., Cassani, G., Blasi, F., and Assoian, R.K. (1985) Proc. Natl. Acad. Sci. U.S. A. 82, 4939-4943). The area within ATF responsible for specific receptor binding has now been identified by the ability of different synthetic peptides corresponding to different regions of the amino terminus of uPA to inhibit receptor binding of 125I-labeled ATF. A peptide corresponding to human [Ala19]uPA-(12-32) resulted in 50% inhibition of ATF binding at 100 nM. Peptides uPA-(18-32) and [Ala13]uPA-(9-20) inhibit at 100 and 2000 microM, respectively. The human peptide uPA-(1-14) and the mouse peptide [Ala20]uPA-(13-33) have no effect on ATF receptor binding. This region of uPA is referred to as the growth factor module since it shares partial amino acid sequence homology (residues 14-33) to epidermal growth factor (EGF). Furthermore, this region of EGF is responsible for binding of EGF to its receptor (Komoriya, A. Hortsch, M., Meyers, C., Smith, M., Kanety, H., and Schlessinger, J. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1351-1355). However, EGF does not inhibit ATF receptor binding. Comparison of the sequences responsible for receptor binding of uPA and EGF indicate that the region of highest homology is between residues 13-19 and 14-20 of human uPA and EGF, respectively. In addition, there is a conservation of the spacings of four cysteines in this module whereas there is no homology between residues 20-30 and 21-33 of uPA and EGF. Thus, residues 20-30 of uPA apparently confer receptor binding specificity, and residues 13-19 provide the proper conformation to the adjacent binding region.     

The biological roles of pyrazines: evidence for a warning odour function

Recently it has been shown that pyrazines are associated with many aposematic, chemically defended insects. We have demonstrated that naive hatchling chicks, when offered drinking water to which 2-methoxy-3-isobutylpyrazine is added, develop a neophobic 'alerting' reaction. The birds are not only capable of forming a conditioned aversion to the pyrazine when it is paired with quinine sulphate but they can also detect it from a distance probably by olfaction. This suggests that birds, a major group of insect predators, can interpret pyrazines as alerting or warning signals. The relationship of pyrazines with other alerting signals, and their evocative qualities are discussed.     

The soluble IL-6 receptors: serum levels and biological function.

IL-6 exerts its biological activities through interaction with specific receptors expressed on the surface of target cells. IL-6 binds first to a low-affinity (10(-9) M) subunit, a 80 kDa glycoprotein also called gp80 or IL-6R alpha. The IL-6/IL-6R alpha complex recruits the signal-transducing b subunit, a 130 kDa glycoprotein called gp130. The association of gp130 with IL-6 and IL-6R alpha leads to the formation of the high-affinity IL-6 receptor complex, to the linkage of two gp130 subunits and to signal transduction. Soluble forms of both receptors have been described and found in biological fluids. Soluble cytokine receptors are generated by either proteolytic cleavage of their membrane moiety or by alternative splicing. Both mechanisms have been described for sIL-6R and sgp130 formation. Interestingly, the association of IL-6 with the soluble form of IL-6R alpha is capable of eliciting a biological response in cells that express only the membrane gp130. This type of activation, called "trans-signalling", renders virtually all cells capable of responding to IL-6/sIL-6R alpha complexes, making for a large new spectrum of IL-6 activities, ranging from the control of the immune response to involvement in pathological states. In this review the biological activities of IL-6 will be considered in the light of new knowledge concerning the association of IL-6 and the soluble IL-6 receptors.     

Effect of mobbing toward predators by the damselfishPomacentrus coelestis (Pisces: Pomacentridae)

Field observations on prey-predator interactions, focusing on mobbing behavior byPomacentrus coelestis, were made in the shallow water of Shirahama, Japan. Within the breeding colony of the damselfish, indirect group mobbing toward 6 ambushers and direct mobbing with physical contact only by nesting males toward a stalker were observed. The direct mobbing toward the stalker (moray eel) is suggested to have involved an element of egg-guarding. Group mobbing was usually released by large and quick attacking motion of the predator. Attack intervals of a predator were much longer after it was mobbed than when it was not mobbed, but there was no significant difference in success ratio of the next attack whether mobbing was elicited or not. Consequently, it is concluded that mobbing effectively reduced future predation risk of each mobber.     

Exploiting big biology: integrating large-scale biological data for function inference.

The amount of data produced by molecular biologists is growing at an exponential rate. Some of the fastest growing sets of data are measurements of gene expression, comparable in quantity only to gene sequences and the vast biological literature. Both gene expression data and sequence data offer hints as to the functions of thousands of newly discovered genes, but neither give complete answers. Therefore, much effort is being focused on integrating these large data sets and combining them with all available functional data to draw inferences about the functions of uncharacterised genes. This review discusses the most pertinent functional data for genome-wide functional inference and describes several methods by which these disparate data types are being integrated.     

A comparative study of the biological properties of Dendroaspis (mamba) snake venoms.

1. The biological properties of twelve samples of venoms from all four species of Dendroaspis (mamba) were investigated. 2. Dendroaspis venoms generally exhibited very low levels of protease, phosphodiesterase and alkaline phosphomonoesterase; low to moderately low level of 5'-nucleotidase and very high hyaluronidase activities, but were devoid of L-amino acid oxidase, phospholipase A, acetylcholinesterase and arginine ester hydrolase activities. The unusual feature in venom enzyme content can be used to distinguish Dendroaspis venoms from other snake venoms. 3. All Dendroaspis venoms did not exhibit hemorrhagic or procoagulant activity. Some Dendroaspis venoms, however, exhibited strong anticoagulant activity. The intravenous median lethal dose of the venoms ranged from 0.5 microgram/g mouse to 4.2 micrograms/g mouse. 4. Venom biological activities are not very useful for the differentiation of the Dendroaspis species. The four Dendroaspis venoms, however, can be differentiated by their venom SDS-polyacrylamide gel electrophoretic patterns.     

The neurotoxins of the sea snake Laticauda schistorhynchus.

Erabutoxins a and b, the major neurotoxins in the venom of the sea snake Laticauda semifasciata, were detected in the venom of Laticauda schistorhynchus. The identity of the toxins was confirmed on the basis of elution position on CM-cellulose column chromatography, disc electrophoretic mobility, amino acid analysis and toxicity measurement.