Probing the role of water in protein conformation and function

Rand, R. P.

doi:10.1098/rstb.2004.1504

Cited by 42 publications

(37 citation statements)

References 44 publications

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“…Glycation of the fibrinogen molecule is unlikely to account for these changes, owing to the short incubation time used. Other possible explanations include alterations in fibrin(ogen) conformation and function induced by changes in 'osmotic stress' [41]. However, further investigation into potential mechanisms is warranted.…”

Section: Discussionmentioning

confidence: 99%

The influence of type 2 diabetes on fibrin structure and function

2005

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Aims/hypothesis: The precise mechanisms underlying the increased risk of cardiovascular disease (CVD) in type 2 diabetes are unclear. Fibrin clot structure has been related to CVD risk in the general population. We therefore assessed this in type 2 diabetic patients as a potential mechanism whereby diabetes influences CVD risk. Methods: Fibrin clots were formed from fibrinogen purified from 150 subjects with type 2 diabetes and varying degrees of glycaemic control (assessed by HbA 1 c), and from 50 matched control subjects. Clot structure was assessed by turbidity, permeation and confocal microscopy. The specific effect of glucose itself was assessed by analysing the structure of clots formed from purified fibrinogen in the presence of increasing concentrations of the sugar. Results: Clots formed by fibrinogen purified from type 2 diabetic subjects had a denser, less porous structure than those from control subjects. The structural changes found were related to the individual's glycaemic control; HbA 1 c correlated negatively with permeation coefficient (K s ) values (indicates clot pore size) (r=−0.57, p<0.0001) and positively with maximum absorbance (indicator of fibre size) (r=0.33, p<0.0001), branch point number (r=0.78, p<0.0001) and fibre density (r=0.63, p<0.0001). The ambient glucose level influenced clot structure; hypo-(<5 mmol) and hyperglycaemia (≥10 mmol/l) were both associated with a reduction in K s values and maximum absorbance, and with increased fibre density and branch point number within clots. Conclusions/ interpretation: The structural differences found to occur in type 2 diabetes and in association with hypo-and hyperglycaemia may confer increased resistance to fibrinolysis, and in consequence contribute to the increase in CVD risk in diabetic patients.

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Section: Discussionmentioning

confidence: 99%

The influence of type 2 diabetes on fibrin structure and function

2005

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“…The usual mechanistic deduction would be that the inhibitor must be displaced from the active site on binding the substrate, and again it seems quite reasonable to apply this picture to water. This is exactly analogous to the treatment of water activity effects in aqueous solution studies, as presented in the accompanying article by Rand (2004). As in these studies, the quantitative dependence of apparent binding constants on water activity can be used to count the numbers of water molecules displaced.…”

Section: How Does Hydration Promote Catalytic Activity?mentioning

confidence: 97%

“…This 'osmotic stress' method has been particularly exploited by Rand and co-workers, and is reviewed in the accompanying paper by Rand (2004). Even high osmotic pressures correspond to fairly small reductions in the mass-action effects of water (e.g.…”

Section: Introductionmentioning

confidence: 99%

What can we learn by studying enzymes in non–aqueous media?

Halling

2004

Phil. Trans. R. Soc. Lond. B

106

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What is the role of water in enzyme structure and function? One approach to answers should come from studies in which the amount of water present is a variable. In the absence of bulk liquid water, effective monitoring of enzyme action requires an alternative fluid medium through which substrates and products may be transported. The past 20 years have seen quite extensive study of enzyme behaviour when reactants are transferred via a bulk phase that is an organic liquid, a supercritical fluid or a gas. Some lipases, at least, remain highly active with only a few, if any, residual water molecules. Many enzymes seem to require larger amounts of water, but still not a liquid water phase. There are hysteresis effects on both the amount of bound water and the observed catalytic activity. Increasing hydration promotes mobility of the enzyme molecule, as revealed by various techniques, and there are correlations with catalytic activity. There are other plausible roles for hydration, such as opening up proton conduction pathways.

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“…(iii) Does the critical lytic tension depend on the strain rate, and thus the strength of the osmotic gradient? Such questions arise beyond the present context of vesicle osmoregulation in other important scenarios where the coupling between the dissipation of osmotic energy and cellular compartmentalization has important biological ramifications (17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Pulsatile lipid vesicles under osmotic stress

Chabanon

Liedberg

et al. 2016

Preprint

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The response of lipid bilayers to osmotic stress is an important part of cellular function. Recent experimental studies showed that when cell-sized giant unilamellar vesicles (GUVs) are exposed to hypotonic media, they respond to the osmotic assault by undergoing a cyclical sequence of swelling and bursting events, coupled to the membrane's compositional degrees of freedom. Here, we establish a fundamental and quantitative understanding of the essential pulsatile behavior of GUVs under hypotonic conditions by advancing a comprehensive theoretical model of vesicle dynamics. The model quantitatively captures the experimentally measured swellburst parameters for single-component GUVs, and reveals that thermal fluctuations enable rate-dependent pore nucleation, driving the dynamics of the swell-burst cycles. We further extract constitutional scaling relationships between the pulsatile dynamics and GUV properties over multiple time scales. Our findings provide a fundamental framework that has the potential to guide future investigations on the non-equilibrium dynamics of vesicles under osmotic stress.

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Probing the role of water in protein conformation and function

Cited by 42 publications

References 44 publications

The influence of type 2 diabetes on fibrin structure and function

The influence of type 2 diabetes on fibrin structure and function

What can we learn by studying enzymes in non–aqueous media?

Pulsatile lipid vesicles under osmotic stress

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