The functions of most genetic circuits require a sufficient degree of cooperativity in the circuit components. Although mechanisms of cooperativity have been studied most extensively in the context of transcriptional initiation control, cooperativity from other processes involved in the operation of the circuits can also play important roles. In this work, we examine a simple kinetic source of ...

The folding of naturally occurring, single-domain proteins is usually well described as a simple, single-exponential process lacking significant trapped states. Here we further explore the hypothesis that the smooth energy landscape this implies, and the rapid kinetics it engenders, arises due to the extraordinary thermodynamic cooperativity of protein folding. Studying Miyazawa-Jernigan lattic...

Changes in [Mg2+] in a millimolar range have a significant inverse effect on the Ca2+- (or Sr2+)activated tension generation of skeletal muscle fibers. Single frog (Rana pipiens) semitendinosus muscle fibers were "skinned" (sarcolemma removed) and contracted isometrically in bathing solutions of varying [Ca2+] or [Sr2+] and [Mg2+] but a constant pH, [MgATP2-], [K+], [CP2-], [CPK], and ionic str...

The number of Ca(2+) channels contributing to the exocytosis of a single neurotransmitter vesicle in a presynaptic terminal has been a question of significant interest and debate, and is important for a full understanding of localized Ca(2+) signaling in general, and synaptic physiology in particular. This is usually estimated by measuring the sensitivity of the neurotransmitter release rate to...

The consensus oestrogen response element (ERE) contains two inverted copies of an AGGTCA consensus hexameric half-site, spaced by three base pairs. It differs from many other hormone response elements, such as consensus thyroid (TREp) and retinoic acid (DR-5 RARE) response elements, only in the relative spacing and orientation of these sequences. In the present study we report values for cooper...

Hexokinase D ('glucokinase') displays positive cooperativity with mannose with the same h values (1.5-1.6) as with glucose but with higher K0.5 values (8 mM at pH 8.0 and 12 mM at pH 7.5). In contrast, fructose and 2-deoxyglucose exhibit Michaelian kinetics [Cárdenas, M. L., Rabajille, E., and Niemeyer, H. (1979) Arch. Biol. Med. Exp. 12, 571-580; Cárdenas, M. L., Rabajille, E., and Niemeyer, H...

Coarse-grained chain simulations were used to study fragments of two homologous proteins of the peripheral subunit-binding domain (PSBD) family, Bacillus stearothermophilus PSBD (E3BD) and Escherichia coli 2-oxo-glutarate dehydrogenase PSBD (BBL). To ascertain a robust rank order of folding cooperativity, native-centric intraprotein interactions were modeled by (i) a common Gō-like potential, a...

Although single-channel Ca microdomains are capable of gating neurotransmitter release in some instances, it is likely that in many cases the microdomains from several open channels overlap to activate vesicle fusion. We describe a mathematical model in which transmitter release is gated by single or overlapping Ca microdomains produced by the opening of nearby Ca channels. This model accounts ...

Background: Recent studies have proposed various sources for the origin of cooperativity in simpliied protein folding models. Important contributions to cooperativity that have been discussed include backbone hydrogen bonding, side-chain packing, and hydrophobic interactions. Related work has also focused on what interactions are responsible for making the free energy of the native structure a ...

The intrinsically active, sn-glycerol-3-phosphate acyltransferase present in membranes prepared from both wild type Escherichia coli and from strains which overproduce the enzyme can be kinetically distinguished from a latent enzyme species which is unmasked by solubilization and reconstitution. Both membrane-associated and solubilized/reconstituted enzyme preparations exhibited cooperativity w...