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Macromolecular Crowding (macromolecular + crowding)

Distribution by Scientific Domains

Chemistry	100%

Selected Abstracts

Binding of rat brain hexokinase to recombinant yeast mitochondria

FEBS JOURNAL, Issue 10 2000
Identification of necessary physico-chemical determinants
The association of rat brain hexokinase with heterologous recombinant yeast mitochondria harboring human porin (Yh) is comparable to that with rat liver mitochondria in terms of cation requirements, cooperativity in binding, and the effect of amphipathic compounds. Mg2+, which is required for hexokinase binding to all mitochondria, can be replaced by other cations. The efficiency of hexokinases, however, depends on the valence of hydrophilic cations, or the partition of hydrophobic cations in the membrane, implying that these act by reducing a prohibitive negative surface charge density on the outer membrane rather than fulfilling a specific structural requirement. Macromolecular crowding (using dextran) has dual effects. Dextran added in excess increases hexokinase binding to yeast mitochondria, according to the porin molecule they harbor. This effect, significant with wild-type yeast mitochondria, is only marginal with Yh as well as rat mitochondria. On the other hand, an increase in the number of hexokinase binding sites on mitochondria is also observed. This increase, moderate in wild-type organelles, is more pronounced with Yh. Finally, dextran, which has no effect on the modulation of hexokinase binding by cations, abolishes the inhibitory effect of amphipathic compounds. Thus, while hexokinase binding to mitochondria is predetermined by the porin molecule, the organization of the latter in the membrane plays a critical role as well, indicative that porin must associate with other mitochondrial components to form competent binding sites on the outer membrane. [source]

The effect of macromolecular crowding on protein aggregation and amyloid fibril formation,

JOURNAL OF MOLECULAR RECOGNITION, Issue 5 2004
Larissa A. Munishkina
Abstract Macromolecular crowding is expected to have several significant effects on protein aggregation; the major effects will be those due to excluded volume and increased viscosity. In this report we summarize data demonstrating that macromolecular crowding may lead to a dramatic acceleration in the rate of protein aggregation and formation of amyloid fibrils, using the protein ,-synuclein. The aggregation of ,-synuclein has been implicated as a critical factor in development of Parkinson's disease. Various types of polymers, from neutral polyethylene glycols and polysaccharides (Ficolls, dextrans) to inert proteins, are shown to accelerate ,-synuclein fibrillation. The stimulation of fibrillation increases with increasing length of polymer, as well as increasing polymer concentration. At lower polymer concentrations (typically up to ,100,mg/ml) the major effect is ascribed to excluded volume, whereas at higher polymer concentrations evidence of opposing viscosity effects become apparent. Pesticides and metals, which are linked to increased risk of Parkinson's disease by epidemiological studies, are shown to accelerate ,-synuclein fibrillation under conditions of molecular crowding. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Chaperonin function,effects of crowding and confinement,

JOURNAL OF MOLECULAR RECOGNITION, Issue 5 2004
Jörg Martin
Abstract Chaperonins assist in the acquisition of native protein structure in the cell by providing a shielded environment for a folding polypeptide chain, generated by the interior surface of their cylindrical structure. The folding chain is isolated from the highly crowded cytoplasm, but at the same time confined within the chaperonin folding cage. Both confinement and macromolecular crowding can affect folding kinetics and yields, the modus operandi of chaperonins and their interaction with their protegés. Recent experimental data, as well as computer simulations, provide increasing evidence that the particular physico-chemical conditions prevailing in the cellular interior have to be taken into account when trying to unravel the processes of cellular protein folding. Copyright © 2004 John Wiley & Sons, Ltd. [source]