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PubMed2004

Interplay between cell division and cell death during TCR triggering.

Cell death is crucial to avoid excessive T cell expansion. During primary T cell expansion in response to pathogen or after vaccination, the amount of foreign Ag determines the degree of clonal amplification and death. Here, we studied the balance between cell proliferation and death, as well as susceptibility to cell death, during TCR triggering. After priming of CD4 T cells from AND-TCR (Vbeta3, Valpha11)-transgenic mice with a high dose of pigeon cytochrome c peptide 88-104, the cell expansion rate was significantly reduced by marked clonal elimination compared to lower Ag doses, whereas the number of cell divisions reached was similar at all Ag doses. TCR re-engagement on activated T cells induced cell death, irrespective of the dose of Ag encountered during primary stimulation. Surprisingly, commitment to apoptosis occurred as early as the first division on all dividing cells both in vitro and in vivo. This phenomenon was highly selective, as activated but non-dividing cells did not undergo cell death, whereas cells that had divided once became susceptible to cell death. These findings have direct implications for the peripheral homeostatic mechanism following Ag challenge and for designing primary/booster vaccine strategies.

Animals↗

PubMed1990

Zone broadening in electrophoresis with special reference to high-performance electrophoresis in capillaries: an interplay between theory and practice.

Approximate equations have been derived for the total (final) zone width (plate height, plate number and resolution) as a function of the width of the starting zone and of the zone broadening caused by diffusion. Joule heat, adsorption and the difference in conductivity (delta kappa) between a solute zone and the surrounding buffer. Two cases are treated: (A) the conductivity differences eliminate entirely or (B) partially, the diffusional broadening at one boundary of a zone. When adsorption is negligible one can derive from these equations the field strength - and for case A also the electrical conductivity - that gives the minimum zone broadening (plate height). Interestingly, at this minimum, contributions to the zone broadening from diffusion. Joule heat and conductivity differences have the ratio 4:1:1 in case A. In case B the ratio between the broadening caused by diffusion (including that caused by conductivity and pH differences) and broadening due to Joule heat is 4:1. The total zone width, plate height and optimal field strength calculated from the derived equations agree satisfactorily with experimental values. A simple method to estimate the variance of the zone broadening caused by the Joule heat led to a formula similar to that calculated mathematically. An appropriate width of the starting zone can be calculated rapidly by means of a simple formula. Following a run the true width can be estimated graphically from measurements of plate heights or zone widths at low field strengths. For high resolution the width of the starting zone usually should not exceed 0.5 mm. A new principle for the design of multi-buffer systems which generate sufficiently narrow starting zones has been developed for carrier-free zone electrophoresis. This zone sharpening method permits application of wide zones of concentrations below the detection limit of the monitor. The diffusion coefficient (D) and the universal parameter D/mu (mu = mobility) appear in many of the equations derived and are often the only variables which are not easily accessible. Simple methods have therefore been developed by which they can be determined with sufficient accuracy. Fortunately, they are raised to the power of 1/5 in many formulas and therefore only a rough estimation is required. True plate numbers (calculated in the absence of electroendosmosis) often differ considerably from apparent plate numbers (calculated in the presence of electroendosmosis). A mathematical relationship between the true and apparent plate numbers has been derived.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrophoresis↗

PubMed2005

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration.

Prostaglandins are hepatoprotective molecules generated in liver regeneration by the rapid induction of cyclooxygenase-2 (COX-2). Cardiotrophin-1 (CT-1) and vascular endothelial growth factor (VEGF) are other hepatoprotective mediators upregulated at 24 hours after partial hepatectomy. The interactions among these molecules during liver regeneration have not yet been defined. Here we show that rats subjected to partial hepatectomy treated with NS-398, a specific COX-2 inhibitor, exhibited cell cycle arrest, increased hepatocyte apoptosis, persistent extracellular signal-regulated kinase (ERK) 1/2 activation, and increased interleukin-6 production. These changes were associated with downregulation of CT-1 and COX-1 and altered pattern of VEGF expression. Administration of an adenovirus encoding CT-1 to NS-398-treated rats restituted normal levels of COX-1, prostaglandins, and VEGF in the liver after partial hepatectomy and restored normal liver regeneration. Furthermore, the stimulation of isolated rat hepatocytes with CT-1 increased COX-1, COX-2, and VEGF messenger RNAs and prostaglandin synthesis. Conversely, the addition of prostaglandin E1 to the culture increased CT-1 and VEGF production. In conclusion, COX-2 activation and production of prostaglandins soon after partial hepatectomy are essential requirements for hepatocyte proliferation and for the correct induction of both CT-1 and VEGF. CT-1 can restore liver regeneration after COX-2 inhibition by increasing VEGF, COX-1 expression, and prostaglandin synthesis.

Animals↗

PubMed1986

A new approach to the evolution of the blastic crisis from chronic myelocytic leukemia: dynamic interplay of cellular alterations and a changing microenvironment.

The mechanisms responsible for the massive hyperplasia and for the blastic crisis in chronic myelocytic leukemia are poorly understood. The most generally accepted hypothesis proposes that this progression is due to the development of genetic instability in the leukemic cells. In particular, the two phases of the disease are believed to reflect different, discrete genetic events. Such events remain undefined as yet, and the causal significance of observed genetic aberrations is not clear. An alternative hypothesis is presented here. It is assumed that the feedback interactions adjust the relative probabilities of maturation and replication of the 'committed' as well as the pluripotent cells, and further that mitotic cells at all stages possess considerable phenotypic adaptability; in particular their self-renewal capacity can vary in response to changes in the cellular composition of the tissue even within a conventionally defined compartment. On this basis, it is shown that chronic leukemia can arise and evolve into the blastic crisis from a progressive decline in a single clonal characteristic--inducibility to maturation. It is shown, with the help of mathematical considerations, how an initial hereditable event in an early hemopoietic cell can cause a disturbance of the tissue which feeds back onto the individual members of the clone, resulting in a cascade of dynamic changes which can lead to blast cell dominance.

Cell Cycle↗

PubMed1991

Dynamic interplay between two copper-titrating components in the transcriptional regulation of cyt c6.

The algal plastidic cytochrome c (cyt c6) is a biochemical equivalent of the copper-containing protein plastocyanin in photosynthetic electron transfer. But generally, cyt c6 accumulates and functions only under conditions (e.g. Cu-deficiency) where holoplastocyanin cannot be synthesized. In studying the regulation of Chlamydomonas reinhardtii cyt c6 expression by Cu we have determined that repression of cyt c6 accumulation occurs at the transcriptional level, and specifically in response to Cu as the metal ion regulator. Complete and sustained repression of cyt c6 transcription requires approximately 9 x 10(6) Cu ions in the medium/cell. Based on the estimated plastocyanin content of algal cells (8 x 10(6) molecules/cell) and the observation that lower ratios of Cu per cell result in only transient repression of cyt c6 transcription, we propose that Cu-dependent transcriptional repression of the gene encoding cyt c6 requires a Cu-binding factor which is titrated by Cu only after the alternate electron transfer catalyst, plastocyanin, has accumulated to the stoichiometry required for photosynthesis. The precise and highly metal-specific, autoregulatory control of cyt c6 levels--directly by Cu, and indirectly by holoplastocyanin--is in keeping with the functional role of cyt c6 as an alternate, although perhaps less preferred, electron transfer catalyst.

Blotting, Northern↗

PubMed1992

Diurnal exposure profile in rats from dietary administration of a chemical (doxazosin) with a short half-life: interplay of age and diurnal feeding pattern.

Doxazosin, an alpha-adrenergic blocking agent, has a plasma half-life in male rats of 1-2 h after i.v. administration. Plasma concentrations of doxazosin were measured in male rats receiving the drug mixed in the diet at dose levels from 5 to 40 mg kg-1. Samples taken at 4-h intervals during the light (0700-1900) and dark phases revealed peak concentrations at 0400 which were only about three times higher than the trough concentrations observed ca. 12 h later. The 24-h area under the curve (AUC) values increased disproportionately with dose and with age from 2 months up to 8 months of age; thereafter they were fairly stable to 24 months of age. This age-related effect may have been due to a reduction in clearance and/or a change in the feeding pattern of the rats. Young rats consumed ca. 84% and old rats only 45% of their daily feed during the nocturnal (active) phase. Given the known diurnal rhythms in absorption, protein binding and enzyme metabolising activity, such a change in feeding pattern with age may have wider toxicokinetic implications.

Adrenergic alpha-Antagonists↗

PubMed1994

Modulation of the Na-H antiport by insulin: interplay between protein kinase C, tyrosine kinase, and protein phosphatases.

The insulin modulation of Na-H antiport in rat hepatocytes was studied using the fluorescent, pH-sensitive intracellular probe, 2',7' bis (carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Our data show that insulin stimulates the Na-H antiport. The dose-response of insulin effect shows a behavior typical of other insulin responses: a maximum in the physiological range (1 nM) and smaller effects at higher and lower hormone concentrations. The time-course of activation is very fast at high hormone concentrations and slow, but reaching a higher value, for the physiological concentrations (0.26 +/- 0.05 and 0.18 +/- 0.022 pH units for 1 nM and 1 microM insulin respectively). The use of phorbol, 12-myristate, 13-acetate (PMA), a potent activator of protein kinase C and its inhibitor staurosporine, and the inhibitor of tyrosine kinase erbstatin analog, suggests that both protein kinase C and tyrosine kinase could be involved in the mechanism leading to Na-H antiport activation by insulin. We suggest that the activation of the antiport involves the two pathways depending on the hormone concentration. In particular, protein kinase C would mediate the effects of high hormone concentrations, acting as a growth factor, since staurosporine fully inhibited insulin 1 microM, but only partially 1 nM effects, and tyrosine kinase would mediate the effect of insulin 1 nM and only partially 1 microM. Okadaic acid 1 microM, a potent inhibitor of protein phosphatases, mimicked the hormone effects on the antiport and abolished the different time-course due to hormone concentration, suggesting a role of kinases and phosphatases in the signal transduction. The effect of all activators was abolished by amiloride analog, 5-(N-ethyl-N-isopropyl) amiloride (EIPA), confirming the specificity of these effects.

Alkaloids↗

PubMed2005

Interaction and functional interplay between endoglin and ALK-1, two components of the endothelial transforming growth factor-beta receptor complex.

Transforming growth factor-beta (TGF-beta) signaling in endothelial cells is able to modulate angiogenesis and vascular remodeling, although the underlying molecular mechanisms remain poorly understood. Endoglin and ALK-1 are components of the TGF-beta receptor complex, predominantly expressed in endothelial cells, and mutations in either endoglin or ALK-1 genes are responsible for the vascular dysplasia known as hereditary hemorrhagic telangiectasia. Here we find that the extracellular and cytoplasmic domains of the auxiliary TGF-beta receptor endoglin interact with ALK-1 (a type I TGF-beta receptor). In addition, endoglin potentiates TGF-beta/ALK1 signaling, with the extracellular domain of endoglin contributing to this functional cooperation between endoglin and ALK-1. By contrast, endoglin appears to interfere with TGF-beta/ALK-5 signaling. These results suggest that the functional association of endoglin with ALK-1 is critical for the endothelial responses to TGF-beta.

Activin Receptors, Type I↗

PubMed2005

The interplay of increased urea synthesis and reduced ammonia production in the African lungfish Protopterus aethiopicus during 46 days of aestivation in a mucus cocoon.

This study was undertaken to test the hypothesis that the rate of urea synthesis in Protopterus aethiopicus was up-regulated to detoxify ammonia during the initial phase of aestivation in air (day 1-day 12), and that a profound suppression of ammonia production occurred at a later phase of aestivation (day 35-day 46) which eliminated the need to sustain the increased rate of urea synthesis. Fasting apparently led to a greater rate of nitrogenous waste excretion in P. aethiopicus in water, which is an indication of increases in production of endogenous ammonia and urea probably as a result of increased proteolysis and amino acid catabolism for energy production. However, 46 days of fasting had no significant effects on the ammonia or urea contents in the muscle, liver, plasma and brain. In contrast, there were significant decreases in the muscle ammonia content in fish after 12, 34 or 46 days of aestivation in air when compared with fish fasting in water. Ammonia was apparently detoxified to urea because urea contents in the muscle, liver, plasma and brain of P. aethiopicus aestivated for 12, 34 or 46 days were significantly greater than the corresponding fasting control; the greatest increases in urea contents occurred during the initial 12 days. There were also significant increases in activities of some of the hepatic ornithine-urea cycle enzymes from fish aestivated for 12 or 46 days. Therefore, contrary to a previous report on P. aethiopicus, our results demonstrated an increase in the estimated rate of urea synthesis (2.8-fold greater than the day 0 fish) in this lungfish during the initial 12 days of aestivation. However, the estimated rate of urea synthesis decreased significantly during the next 34 days. Between day 35 and day 46 (12 days), urea synthesis apparently decreased to 42% of the day 0 control value, and this is the first report of such a phenomenon in African lungfish undergoing aestivation. On the other hand, the estimated rate of ammonia production in P. aethiopicus increased slightly (14.7%) during the initial 12 days of aestivation as compared with that in the day 0 fish. By contrast, the estimated rate of ammonia production decreased by 84% during the final 12 days of aestivation (day 35-day 46) compared with the day 0 value. Therefore, it can be concluded that P. aethiopicus depended mainly on increased urea synthesis to ameliorate ammonia toxicity during the initial phase of aestivation, but during prolonged aestivation, it suppressed ammonia production profoundly, eliminating the need to increase urea synthesis which is energy-intensive.

Amino Acids↗

PubMed1993

Interplay between superantigens and the immune system.

Superantigens interact with the immune system by binding to major histocompatibility complex (MHC) class II proteins and activating T cells through the variable region of the T cell receptor beta-chain. Through this means they can cause massive proliferation and then death of a large proportion of T cells. Superantigens are produced by bacteria, mycoplasmas, retroviruses, and probably by other organisms. In some cases, the superantigen is crucial to the organism's life cycle. Mouse mammary tumor virus disseminates by activating T cells which stimulate the proliferation of B cells harboring the virus. In other cases, the superantigen may be responsible for the pathogenesis of the infection, such as in the case of Toxic Shock Syndrome. In this article, we review information on the diseases in which superantigens are involved, and the mechanisms by which the superantigens interact with T cell receptor and class II molecules.

Animals↗

PubMed1981

Interplay of cell and serum immunologic markers in chronic persistent or active hepatitis B.

Immunologic markers associated with hepatitis B virus (HBV) infection (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-delta) were tested by radioimmunoassay of serum from chronic hepatitis patients. The corresponding liver biopsy samples were examined for the presence of HBsAg, HBcAg, and delta antigen in the cells by direct immunofluorescence and by electron microscopy. Seventy patients were selected for the presence of both circulating HBsAg and anti-HBc. Comparison of chronic persistent (CPH) and chronic active (CAH) hepatitis showed a significantly greater frequency of intracytoplasmic HBsAg in CPH, especially in the absence of intranuclear HBsAg, and a greater frequency of intranuclear delta antigen and/or circulating anti-delta in CAH. The delta/anti-delta system was almost systematically associated with serum anti-HBe. At variance with HBeAg/anti-HBe, delta/anti-delta found significantly more frequently in patients originating from Southern rather than from Northern or Central Italy. The prevalence of both these immunologic systems was related to the age of the patients.

Adolescent↗

PubMed2025

Dynamic Interplay Between miR-133a and RBMX During Dengue Virus Infection.

Viruses are obligate intracellular pathogens with limited genome capacity, relying entirely on host factors and cellular machinery for sustainable infection. In the present study, we demonstrate that dengue infection modulates the expression of RBMX (an RNA-binding protein) and miR-133a. Viral infection elevates the expression of the RBMX gene while downregulates the level of miR-133a. Additionally, Targetscan tool analysis shows that miR-133a possesses a potential binding site in the 3'UTR region of the RBMX gene, and our luciferase data indicate the miR-133a-mediated regulation of RBMX expression. Intriguingly, our time point study in Huh7 cells overexpressing the synthetic form of miR-133a mimic and inhibitor indicates the convoluted interaction between miR-133a and RBMX regulation during DENV infection. After 24 h postinfection (hpi), miR-133a significantly suppresses both the RBMX expression and viral RNA levels, acting as an antiviral agent by targeting the expression of the RBMX gene. Additionally, our immunoprecipitation result suggested the central role of DENV 3'UTR in regulating the expression of both RBMX and miR-133a. Furthermore, our study on RBMX Overexpression illuminates the vital function of RBMX protein in the DENV life cycle. Overexpression of the RBMX gene in ivermectin-pretreated cells partially rescues viral replication. This comprehensive study explicates the dynamic miRNA/RBPs regulatory axis during DENV pathogenesis.

MicroRNAs↗

PubMed2004

Interplay among platelet-activating factor, oxidative stress, and group I metabotropic glutamate receptors modulates neuronal survival.

Platelet-activating factor (PAF) is a potent phospholipid messenger in the nervous system that participates in synaptic plasticity and in pathologic processes, including neurodegeneration. Oxidative stress plays important roles in neuronal cell death. To define the interaction between PAF and oxidative radicals in neuronal death, we studied the effects of PAF in the presence of oxidative radicals in primary neurons in culture. Exogenous PAF (50 microM) caused PAF receptor-independent injury to neurons. A nonneurotoxic PAF concentration (500 nM) potentiated neuronal death caused by hydrogen peroxide as determined by lactate dehydrogenase (LDH) assay, Hoechst staining, and TUNEL analysis, but it did not potentiate neuronal death caused by menadione, a superoxide donor, or by the nitric oxide donors 3-morpholino-sydnonimine (SIN-1) and sodium nitroprusside (SNP). This potentiation of the hydrogen peroxide effect was selectively blocked by a PAF membrane-receptor antagonist, BN52021 (5 microM). The neurotoxic effect of PAF and hydrogen peroxide was also completely blocked by ebselen and partially decreased by pretreatment with (S)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR) agonist. This study suggests that PAF-receptor antagonists may be useful for neuroprotection. A similar effect might also be obtained with group I mGluR agonists, probably by way of a different underlying mechanism.

Animals↗

PubMed1995

Control of neuronal morphology in vitro: interplay between adhesive substrate forces and molecular instruction.

Among the factors which influence neuronal morphology, the degree of substrate adhesivity has been suggested to play an important role in the growth and guidance of neurites. The present study was undertaken to investigate apparently contradictory results relating substrate adhesivity to the extent of neurite outgrowth. By using substrates coated with different concentrations of polyornithine to vary adhesivity, we could show that intermediate levels of neuron-to-substrate adhesive strength favored neurite outgrowth more than substrates of high or low adhesivity. However, when neurons were plated on substrates derived from the extracellular matrix, the strength of neuron-to-substrate adhesion was important for the growth of dendrite-like minor neurites, but not for the extension of axon-like major neurites, which grew independently of adhesive forces. On substrates of the cell adhesion molecule L1, growth of both major and minor neurites was adhesion-independent. Finally, in the presence of tenascin added to the culture medium, neurite growth was inhibited irrespective of the adhesivity of the substrate and the presence of substrate-bound extracellular matrix molecules or L1. These observations suggest that intermediate forces of adhesivity favor neurite growth in general, but that purely adhesive forces can be dominated by specific molecular instructions which differentially affect growth of major and minor neurites in positive and negative ways.

Animals↗

PubMed2004

A simple molecule with a complex crystal structure: interplay of 31P solid-state NMR spectroscopy and single-crystal x-ray diffraction in the structure determination of a ruthenium diphosphine diamine complex.

A comprehensive 31P solid-state NMR study of Ru(eta1-Ph2PCH2CH2OCH3)2(eta2-en)Cl2 (en = ethylenediamine) (1), by 1D (contact time variation, inversion-recovery, SPARTAN) and 2D techniques (homonuclear J-resolved, SECSY) indicated that the crystal structure of 1 should be complex. The single-crystal x-ray structure determination confirmed the presence of eight independent molecules in the asymmetric unit, with 31P isotropic chemical shifts in the range 27.3-40.1 ppm, while the spans of the phosphorus chemical shift tensors are of the order of 170 ppm. Based on unique structural features and NMR data, one molecule has been tentatively assigned.

Algorithms↗

PubMed2007

Large-scale chromatin remodeling in germinal vesicle bovine oocytes: interplay with gap junction functionality and developmental competence.

In mammals, oocyte acquires a series of competencies sequentially during folliculogenesis that play critical roles at fertilization and early stages of embryonic development. In mouse, chromatin in germinal vesicle (GV) undergoes dynamic changes during oocyte growth and its progressive condensation has been related to the achievement of developmental potential. Cumulus cells are essential for the acquisition of meiotic competence and play a role in chromatin remodeling during oocyte growth. This study is aimed to characterize the chromatin configuration of growing and fully grown bovine oocytes, the status of communications between oocyte and cumulus cells and oocyte developmental potential. Following nuclear staining, we identified four discrete stages of GV, characterized by an increase of chromatin condensation. GV0 stage represented 82% of growing oocytes and it was absent in fully grown oocytes. GV1, GV2, and GV3 represented, respectively, 24, 31, and 45% of fully grown oocytes. Our data indicated a moderate but significant increase in oocyte diameter between GV0 and GV3 stage. By dye coupling assay the 98% of GV0 oocytes showed fully open communications while the number of oocytes with functionally closed communications with cumulus cells was significantly higher in GV3 group than GV1 and GV2. However, GV0 oocytes were unable to progress through metaphase II while GV2 and GV3 showed the highest developmental capability. We conclude that in bovine, the progressive chromatin condensation is related to the sequential achievement of meiotic and embryonic developmental competencies during oocyte growth and differentiation. Moreover, gap-junction-mediated communications between oocyte and cumulus cells could be implicated in modulating the chromatin remodeling process.

Animals↗

PubMed2002

Melatonin and prostate cancer cell proliferation: interplay with castration, epidermal growth factor, and androgen sensitivity.

BACKGROUND: Potential modulatory effects of melatonin on the proliferation of androgen-sensitive LNCaP and androgen-insensitive PC-3 and DU 145 prostate cancer cells were reported recently. In this study, we investigated the effects of combined melatonin and castration on LNCaP tumor growth in vivo, the interactions between melatonin and epidermal growth factor (EGF) on LNCaP cell proliferation, and melatonin actions on the proliferation of PC-3 and DU 145 cells. METHODS: Tumor development and growth in castrated nude mice inoculated with LNCaP cells or in intact animals inoculated with DU 145 cells, with or without daily melatonin treatment, were monitored by observation and caliper measurement. MT(1) receptor expression in native or transfected prostate cancer cell lines was examined by immunocytochemistry or 2-[(125)I]iodomelatonin binding. Cyclin D1 expression in LNCaP cells was assessed by Western blotting, and cell proliferation was measured by thymidine incorporation and/or cell count. RESULTS: Melatonin treatment was associated with further decreases in LNCaP tumor incidence and growth rate in castrated nude mice. Melatonin and 2-iodomelatonin (a melatonin receptor agonist) attenuated EGF-stimulated increases in LNCaP cell proliferation and cyclin D1 levels. Melatonin had no effect on the proliferation or growth of MT(1) receptor-expressing DU 145 cells, and of PC-3 cells in which MT(1) receptor protein was undetectable. The proliferation of transfected PC-3 cells expressing MT(1) receptor was unaffected by 2-iodomelatonin. CONCLUSION: Together with previous data, the present results indicate synergistic action of melatonin and castration in inhibiting the growth of androgen-sensitive LNCaP tumor. Androgen-sensitive prostate cancer cell proliferation may be modulated by opposite changes in cyclin D1 levels induced by activated MT(1) and EGF receptors. In androgen-insensitive prostate cancer cells, MT(1) receptor-mediated signal transduction may become defective not only through changes in membrane receptor protein expression and/or functions, but also by means of alterations in downstream postreceptor signaling events.

Androgens↗

PubMed2003

Contact order dependent protein folding rates: kinetic consequences of a cooperative interplay between favorable nonlocal interactions and local conformational preferences.

Physical mechanisms underlying the empirical correlation between relative contact order (CO) and folding rate among naturally occurring small single-domain proteins are investigated by evaluating postulated interaction schemes for a set of three-dimensional 27mer lattice protein models with 97 different CO values. Many-body interactions are constructed such that contact energies become more favorable when short chain segments sequentially adjacent to the contacting residues adopt native-like conformations. At a given interaction strength, this scheme leads to folding rates that are logarithmically well correlated with CO (correlation coefficient r = 0.914) and span more than 2.5 orders of magnitude, whereas folding rates of the corresponding Gō models with additive contact energies have much less logarithmic correlation with CO and span only approximately one order of magnitude. The present protein chain models also exhibit calorimetric cooperativity and linear chevron plots similar to that observed experimentally for proteins with apparent simple two-state folding/unfolding kinetics. Thus, our findings suggest that CO-dependent folding rates of real proteins may arise partly from a significant positive coupling between nonlocal contact favorabilities and local conformational preferences.

Kinetics↗