Design principles of adaptive immune systems

Both jawless vertebrates, such as lampreys and hagfish, and jawed vertebrates (encompassing species as diverse as sharks and humans) have an adaptive immune system that is based on somatically diversified and clonally expressed antigen receptors. Although the molecular nature of the antigen receptors and the mechanisms of their assembly are different, recent findings suggest that the general design principles underlying the two adaptive immune systems are surprisingly similar. The identification of such commonalities promises to further our understanding of the mammalian immune system and to inspire the development of new strategies for medical interventions targeting the consequences of faulty immune functions.     

Postradiation changes in the systems of active transport of ions in the CNS. Energy requirements for active transport

A study was made of the effect of irradiation with a superlethal dose of 9.288 C/kg on oxidative phosphorylation in morphologically and functionally different parts of the central nervous system. The CNS-syndrome was shown to develop against the background of a pronounced injury to energy processes in the brain. It is supposed that the impairment of the energy supply of active ion transport systems plays an important role in the dysfunction of the brain induced by high-level radiation.     

Contributions to the theory of active transport: III. The effect of drugs on active transport systems

The addition of a drug to a system which contains an active transport mechanism may produce a large number of effects on both the active transport mechanism and the permeability of the system. A general model of such a system is presented, and various possible results of the drug's addition are discussed. Methods of experimentally separating these effects on the active transport mechanism and the permeabilities of the system are then listed and analyzed.     

Immobilized cycling enzyme active transport systems. pH feedback control

Active transport can be induced by applying a pH gradient across a membrane containing a homogeneous mixture of two cycling enzymes. When the two reactions are inversely 'pH active', one producing protons and the other consuming them, a pH feedback control of the functional structure occurs and the active transport function of the membrane can be either stabilized or inhibited according to whether the endogenic pH modifications tend to enhance or reduce the exergonic pH gradient. When it is stabilized, the system looks like a thin active layer surrounded by two diffusive layers, leading to a fairly good model for biological transport systems. Under particular conditions, signals can be emitted.     

Ordered binding model as a general mechanistic mechanism for secondary active transport systems.

The mechanistic mechanism of secondary active transport processes has not been fully elucidated. Based on substrate binding studies dependent on coupling cation concentrations of the glutamate, melibiose, lactose and proline transport carriers in Escherichia coli, the ordered binding mechanism was proposed as the energy coupling mechanism of the transport systems. This ordered binding mechanism satisfactorily explained the properties of the secondary active transport systems. Thus, this mechanism as the general energy coupling mechanism for the transport systems is discussed.     

Secondary active transport

Secondary active transport is defined as the transport of a solute in the direction of its increasing electrochemical potential coupled to the facilitated diffusion of a second solute (usually an ion) in the direction of its decreasing electrochemical potential. The coupling agents are membrane proteins (carriers), each of which catalyzes simultaneously the facilitated diffusion of the driving ion and the active transport of a given solute. The review starts with some considerations on the energetics followed by a presentation of the kinetics of secondary active transport. Examples of information which may be gained by such studies are discussed. In the second part, some examples of secondary transport are given; we also describe the characteristics of the corresponding carriers. The various transport systems presented are: the D-glucose/Na+ symport in brush-border membranes, the lactose/H+ symport in E. coli, the Na+/H+ antiport, the different transport systems in the inner mitochondrial membrane.     

Kinetic analysis of active membrane transport systems: equations for net velocity and isotope exchange.

Equations for the initial net velocity and for isotope exchange velocities in active membrane transport systems are presented. The equations are expressed entirely in terms of kinetic constants which are experimentally determinable from appropriate reciprocal plots, and replots of slope and intercept (for net velocity) or 1/Δslope and 1/Δintercept (for isotope exchange). The equations and plots are equally applicable to a soluble iso uni uni enzyme system.The effect of pH on sulfate transport by an ATP-sulfurylase negative mutant of Penicillium notatum was analyzed assuming that ³⁵SO₄²⁻ and H⁺ are cosubstrates of the transport system. The kinetics are consistent with an ordered addition to the carrier of one H⁺ ion followed by ³⁵SO₄²⁻, with H⁺ in equilibrium with the carrier and the carrier-H⁺ complex.     

Facilitated diffusion and active transport systems for glucose in metacercariae of Clinostomum marginatum (Digenea)

Metacercariae of Clinostomum marginatum excysted from yellow perch, Perca flavescens, appear to have two systems for transporting glucose across the tegument, facilitated diffusion and active transport. These systems were distinguished by their differential sensitivities to Na⁺, phlorizin and phloretin. In Ringer's saline for cold-blooded vertebrates, 0.1 mm phlorizin and phloretin were incomplete, but similarly effective inhibitors of glucose uptake in 3 min incubations; worms accumulated in 1 h nonmetabolized 3-O-methylglucose against an apparent concentration difference demonstrating the active transport component. In Na⁺-free saline, phlorizin sensitivity and active transport capacity disappeared, but a phloretin sensitive, Na⁺-independent component remained. The V_max and K₁ of the Na⁺-independent system were 3.0 ± 0.54 μmol/g ethanol-extracted dry wt/h, and 0.8 ± 0.36 mm, respectively. V_max and K₁ of the Na⁺-dependent system, estimated by subtracting the Na⁺-independent values from those obtained in Ringer's saline, were 1.3 ± 0.27 μ mol/g ethanol-extracted dry wt/h, and0.7 ± 0.36mm, respectively.     

Design principles for robust oscillatory behavior

Oscillatory responses are ubiquitous in regulatory networks of living organisms, a fact that has led to extensive efforts to study and replicate the circuits involved. However, to date, design principles that underlie the robustness of natural oscillators are not completely known. Here we study a three-component enzymatic network model in order to determine the topological requirements for robust oscillation. First, by simulating every possible topological arrangement and varying their parameter values, we demonstrate that robust oscillators can be obtained by augmenting the number of both negative feedback loops and positive autoregulations while maintaining an appropriate balance of positive and negative interactions. We then identify network motifs, whose presence in more complex topologies is a necessary condition for obtaining oscillatory responses. Finally, we pinpoint a series of simple architectural patterns that progressively render more robust oscillators. Together, these findings can help in the design of more reliable synthetic biomolecular networks and may also have implications in the understanding of other oscillatory systems.

Electronic supplementary material

The online version of this article (doi:10.1007/s11693-015-9178-6) contains supplementary material, which is available to authorized users.     

Engineering design principles for organelle size control systems

Organelle size is an important determinant of organelle function, and for this reason cells have evolved mechanisms to control and adjust organelle size in the face of intrinsic biological fluctuations. Size control systems have been found that employ a variety of distinct mechanisms, which fall into a small number of classes. Each class represents a design principle by which artificial size controllers could be developed for synthetic biology applications.     

Atomic structures of periplasmic binding proteins and the high-affinity active transport systems in bacteria

We have determined and refined the X-ray crystal structures of six periplasmic binding proteins that serve as initial receptors for the osmotic-shock sensitive, active transport of L-arabinose, D-galactose/D-glucose, maltose, sulphate, leucine/isoleucine/valine and leucine. The tertiary structures and atomic interactions between proteins and ligands show common features that are important for understanding the function of the binding proteins. All six structures are ellipsoidal, consisting of two similar, globular domains. The ligand-binding site is located deep in the cleft between the two domains. Irrespective of the nature of the ligand (e.g. saccharide, sulphate dianion or leucine zwitterion), the specificities and affinities of the binding sites are achieved mainly through hydrogen-bonding interactions. Binding of ligands induces a large protein conformational change. Three different structures have been observed among the binding proteins: unliganded 'open cleft', liganded 'open cleft', and liganded 'closed cleft'. Here we discuss the functions of binding proteins in the light of numerous crystallographic and ligand-binding studies and propose a mechanism for the binding protein-dependent, high-affinity active transport.     

Differences of affinity and energetics of the active transport systems for amino acids in Chang liver cells.

The plasma membrane of Chang liver cells was shown to have at least two distinct active transport systems, one with preferential affinity for glycine and one for leucine. The uptakes of glycine and leucine were specificially inhibited by Me-AIB and b-BCH, respectively. The uptake of glycine decreased remarkably within 10 min on incubation with DNP (2 mM), KCN (5 mM), and malonate (20 mM) under aerobic conditions, along with a decrease of cellular ATP concentration to as low as 1/4 of normal, while the uptake of leucine was not depressed under these conditions. Leucine uptake was, however, greatly reduced within 10 min on incubation with DNP plus ICH2CONH2 (5 mM), when the cellular ATP was estimated at about 0.066 mM. The active transport of leucine, but not that of glycine, was accompanied by further acidification of the intracellular fluid, which was lower in pH than the extracellular fluid by approximately 0.3 unit without addition of amino acid to the medium.