What is the function of protein carboxyl methylation?

The following functions of protein carboxyl methylation seem to be reasonably well established: Multiple, stoichiometric methylation of chemotactic receptors in bacteria at glutamyl residues serves as one (but not the only) adaptation mechanism of the transduction chain to constant background levels of chemotactic stimuli. Stoichiometric methylation of hormones and hormone carrier proteins plays a role in hormone storage and secretion by the pituitary gland. Substoichiometric methylation at D-aspartyl residues is involved in a repair mechanism of aged proteins. Stoichiometric methylation of calmodulin modulates the sensitivity of calmodulin-dependent processes to calcium. Research of the past 3 years has indicated that in order to demonstrate an involvement of methylation in the coupling of surface receptors to intracellular events three new criteria have to be met: (a) the cell should possess a protein carboxyl methylase with relatively narrow substrate specificity; (b) methylation should take place at L-amino acid residues; (c) the methyl accepting proteins should be methylated in a stoichiometric fashion.     

What constitutes the signal for the initiation of protein synthesis on Escherichia coli mRNAs?

Small DNA fragments (60 to 80 nucleotides), randomly obtained from a collection of 14 catabolic, biosynthetic or regulatory Escherichia coli genes, have been shot-gun cloned in place of the lacZ ribosome binding site. A total of 47 recombinants showing substantial beta-galactosidase synthesis (at least 1/30th of the wild-type) were isolated, and their newly acquired translational starts were characterized. Of these, 46 were found to carry a ribosome binding site from one of the original genes, and only one, a non-natural start. Moreover, 12 out of the 14 natural starts were found. The two that were not found are the only ones lacking a Shine-Dalgarno element. So, real starts are generally active in the lac mRNA, whereas the many sites (approx. 100 in this gene collection) that carry a Shine-Dalgarno element followed by AUG or GUG but are located in intra- or intergenic regions, or on non-transcribed strands, are inactive. I conclude that: (1) these "false" starts, being strongly discriminated against in the lac message, are presumably also inactive in their original mRNAs; (2) the discriminating information, being portable from one mRNA to another, must be contained within a small DNA region surrounding the starts. Indeed, I further show that it generally lies within a sequence of about 35 nucleotides bracketing real starts; and (3) this information must have a larger effect on initiation than the exact structure of the mRNA, because the discrimination persists despite a complete change of this structure. Previous statistical analysis has shown that real starts differ from false starts in having a non-random sequence composition from nucleotides -20 to +15 with respect to the start. To uncover whether these biases constitute the discriminating information or simply reflect coding constraints, translational starts were randomly searched in eukaryotic, largely non-coding, DNA. These "eukaryotic" starts all have an in-phase AUG or GUG, preceded by a typical Shine-Dalgarno sequence; outside these elements, the initiator region is strikingly rich in A, and poor in C. These biases match those found around real starts, demonstrating that they are indeed part of the initiation signal. Finally, I describe a simple procedure for introducing any DNA fragment in place of the lac operator site on the E. coli chromosome.     

What is the function of centrioles?

The function of centrioles has been controversial and remains incompletely resolved. This is because centrioles, in and of themselves, do not directly perform any physiological activity. Instead, their role is only to act as a jig or breadboard onto which other functional structures can be built. Centrioles are primarily involved in forming two structures-centrosomes and cilia. Centrioles bias the position of spindle pole formation, but because spindle poles can self-organize, the function of the centriole in mitosis is not obligatory. Consequently, lack of centrioles does not generally prevent mitosis, although recent experiments suggest acentriolar spindles have reduced fidelity of chromosome segregation. In contrast, centrioles are absolutely required for the assembly of cilia, including primary cilia that act as cellular antennae. Consistent with this requirement, it is now becoming clear that many ciliary diseases, including nephronophthisis, Bardet-Biedl syndrome, Meckel Syndrome, and Oral-Facial-Digital syndrome, are caused by defects in centriole-associated proteins.     

What is the function of the claustrum?

The claustrum is a thin, irregular, sheet-like neuronal structure hidden beneath the inner surface of the neocortex in the general region of the insula. Its function is enigmatic. Its anatomy is quite remarkable in that it receives input from almost all regions of cortex and projects back to almost all regions of cortex. We here briefly summarize what is known about the claustrum, speculate on its possible relationship to the processes that give rise to integrated conscious percepts, propose mechanisms that enable information to travel widely within the claustrum and discuss experiments to address these questions.     

What is known about phytohormones in halophytes? A review

Phytohormones participate in many aspects of the plant life cycle, including responses to biotic and abiotic stresses. They play a key role in plant responses to the environment with direct bearing on a plant’s fitness for adaptation and reproduction. In recent years, there have been major advances in our understanding of the role of phytohormones in halophytic plants. The variability in maximal salinity level that halophytes can tolerate makes it difficult to characterize the specific traits responsible for salt tolerance. However, the most evident effect of salinity is growth disturbance, and growth is directly governed by phytohormones. Phytohormones such as abscisic acid, salicylic acid ethylene and jasmonates are traditionally related to stress responses, while the involvement of cytokinins, gibberellins and auxins has started to be analyzed. Polyamines, although they can’t be considered phytohormones because of the high concentrations required for cell responses, have been proposed as a new category of plant growth regulators involved in several plant processes and stress responses. This review integrates the advances in the knowledge about phytohormones in halophytes and their participation in salt tolerance.     

On the function of the various quinone species in Escherichia coli

The respiratory chain of Escherichia?coli contains three quinones. Menaquinone and demethylmenaquinone have low midpoint potentials and are involved in anaerobic respiration, while ubiquinone, which has a high midpoint potential, is involved in aerobic and nitrate respiration. Here, we report that demethylmenaquinone plays a role not only in trimethylaminooxide-, dimethylsulfoxide- and fumarate-dependent respiration, but also in aerobic respiration. Furthermore, we demonstrate that demethylmenaquinone serves as an electron acceptor for oxidation of succinate to fumarate, and that all three quinol oxidases of E.?coli accept electrons from this naphtoquinone derivative.     

What is the benefit to Escherichia coli of having multiple toxin-antitoxin systems in its genome?

The Escherichia coli K-12 chromosome encodes at least five proteic toxin-antitoxin (TA) systems. The mazEF and relBE systems have been extensively characterized and were proposed to be general stress response modules. On one hand, mazEF was proposed to act as a programmed cell death system that is triggered by a variety of stresses. On the other hand, relBE and mazEF were proposed to serve as growth modulators that induce a dormancy state during amino acid starvation. These conflicting hypotheses led us to test a possible synergetic effect of the five characterized E. coli TA systems on stress response. We compared the behavior of a wild-type strain and its derivative devoid of the five TA systems under various stress conditions. We were unable to detect TA-dependent programmed cell death under any of these conditions, even under conditions previously reported to induce it. Thus, our results rule out the programmed-cell-death hypothesis. Moreover, the presence of the five TA systems advantaged neither recovery from the different stresses nor cell growth under nutrient-limited conditions in competition experiments. This casts a doubt on whether TA systems significantly influence bacterial fitness and competitiveness during non-steady-state growth conditions.     

What Is the Role of ε in the Escherichia coli ATP Synthase?

The ATP synthase from Escherichia coli is a prototype of the ATP synthases that are found in many bacteria, in the mitochondria of eukaryotes, and in the chloroplasts of plants. It contains eight different types of subunits that have traditionally been divided into F₁, a water-soluble catalytic sector, and F_o, a membrane-bound ion transporting sector. In the current rotary model for ATP synthesis, the subunits can be divided into rotor and stator subunits. Several lines of evidence indicate that is one of the three rotor subunits, which rotate through 360 degrees. The three-dimensional structure of is known and its interactions with other subunits have been explored by several approaches. In light of recent work by our group and that of others, the role of in the ATP synthase from E. coli is discussed.     

What is the function of receptor and membrane endocytosis at the postsynaptic neuron?

This paper explores the implications of certain new developments in cell biology upon neuroscience. Until recently it was thought that neurotransmitters and neuromodulators had only one function, which was to stimulate their specific receptors at the cell surface. From here on, all activity was supposed to be effected by postsynaptic cascades. The discovery that membrane components, particularly G-protein-linked receptors, are not static but are subject to a massive and complex process of continual endocytosis, processing in the endosome system and recycling back to the external membrane, raises the question of its functional significance. In addition, it has been found that many neuromodulators such as polypeptides have their main locus of action inside the postsynaptic neuron. This review covers the role of the endocytic mechanism on receptor desensitization and resensitization, synaptic reorganization and plasticity synaptic scaling and the possible repair of oxidative damage. The possible involvement of this system in Alzheimer's disease is discussed.     

What is the function of MSP-I on the malaria merozoite?

In the absence o f any clear enzymatic activity, attempts to define the role of merozoite surface protein-I have focused mainly on analysis of its structure, on its interaction with the immune system and on binding assays. But how does our knowledge of the structure o f this protein contribute to functional studies? Are there data to suggest a role in the evasion of effective host immune responses? Binding studies have used the intact protein or various fragments and peptides, but do such approaches provide a reliable indicator of function? In this article, Tony Holder and Mike Blackman review these areas.     

What is the protein design alphabet?

Selecting a protein sequence that corresponds to a specific three-dimensional protein structure is known as the protein design problem. One principal bottleneck in solving this problem is our lack of knowledge of precise atomic interactions. Using a simple model of amino acid interactions, we determine three crucial factors that are important for solving the protein design problem. Among these factors is the protein alphabet-a set of sequence elements that encodes protein structure. Our model predicts that alphabet size is independent of protein length, suggesting the possibility of designing a protein of arbitrary length with the natural protein alphabet. We also find that protein alphabet size is governed by protein structural properties and the energetic properties of the protein alphabet units. We discover that the usage of average types of amino acid in proteins is less than expected if amino acids were chosen randomly with naturally occurring frequencies. We propose three possible scenarios that account for amino acid underusage in proteins. These scenarios suggest the possibility that amino acids themselves might not constitute the alphabet of natural proteins.     

What is the role of PACAP in gonadotrope function?

Strong evidence in favor of a direct action of hypothalamic PACAP at the pituitary to modulate gonadotrope function has been acquired mainly by in vitro studies using cultured pituitary cells or gonadotrope cell lines. In particular, PACAP has been shown to cooperate with GnRH, the primary regulator of gonadotropes, to regulate/modulate gonadotropin subunit gene expression, gonadotropin release as well as gonadotrope responsiveness. These effects of PACAP appear to be due essentially to its high potent stimulatory action on the cAMP/protein kinase pathway. Ensuing mechanisms include signaling cross-talk and/or enhanced gene expression within gonadotropes. PACAP may also indirectly operate on these cells through paracrine mechanisms. While PACAP has long been viewed as a hypophysiotropic factor, a locally produced PACAP has also been described. Interestingly, both appear similarly up-regulated at proestrus of the reproductive cycle in female rats. Further in vivo investigation is now necessary to ascertain the physiological relevance of the observed pituitary PACAP effects and especially to evaluate the respective contribution of hypothalamic and pituitary PACAP in the dynamic control of gonadotrope function.     

What is the role of thermodynamics on protein stability?

The most challenging and emerging field of biotechnology is the tailoring of proteins to attain the desired characteristic properties. In order to increase the stability of proteins and to study the function of proteins, the mechanism by which proteins fold and unfold should be known. It has been debated for a long time how exactly the linear form of a protein is converted into a stable 3-dimensional structure. The literature showed that many theories support the fact that protein folding is a thermodynamically controlled process. It is also possible to predict the mechanism of protein deactivation and stability to an extent from thermodynamic studies. This article reviewed various theories that have been proposed to explain the process of protein folding after its biosynthesis in ribosomes. The theories of the determination of the thermodynamic properties and the interpretation of thermodynamic data of protein stability are also discussed in this article.     

What limits the efficiency of double-strand break-dependent stress-induced mutation in Escherichia coli?

Stress-induced mutation is a collection of molecular mechanisms in bacterial, yeast and human cells that promote mutagenesis specifically when cells are maladapted to their environment, i.e. when they are stressed. Here, we review one molecular mechanism: double-strand break (DSB)-dependent stress-induced mutagenesis described in starving Escherichia coli. In it, the otherwise high-fidelity process of DSB repair by homologous recombination is switched to an error-prone mode under the control of the RpoS general stress response, which licenses the use of error-prone DNA polymerase, DinB, in DSB repair. This mechanism requires DSB repair proteins, RpoS, the SOS response and DinB. This pathway underlies half of spontaneous chromosomal frameshift and base substitution mutations in starving E. coli [Proc Natl Acad Sci USA 2011;108:13659-13664], yet appeared less efficient in chromosomal than F' plasmid-borne genes. Here, we demonstrate and quantify DSB-dependent stress-induced reversion of a chromosomal lac allele with DSBs supplied by I-SceI double-strand endonuclease. I-SceI-induced reversion of this allele was previously studied in an F'. We compare the efficiencies of mutagenesis in the two locations. When we account for contributions of an F'-borne extra dinB gene, strain background differences, and bypass considerations of rates of spontaneous DNA breakage by providing I-SceI cuts, the chromosome is still ～100 times less active than F. We suggest that availability of a homologous partner molecule for recombinational break repair may be limiting. That partner could be a duplicated chromosomal segment or sister chromosome.