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Crowded with macromolecules, cells create a 'charge'

Proteins covered in positive charges stick to ribosomes, while most water-soluble proteins carry negative charges...

Prokaryote cells, such as the bacteria E. Coli and Streptocccus, are one celled without any internal membranes surrounding their interior structures. Even their one circular piece of double-strand DNA is not enclosed within a true membrane. So being crowded with large molecules, the movement of proteins through prokaryote cell cytoplasm is very difficult.
"Cell cytoplasm is a bustling place that affects protein and RNA diffusion. Except for some proteins, where we could not find this correlation. So we set out to investigate why."

Bert Poolman PhD, Professor, Piochemistry, University of Groningen, Netherlands.

Poolman's group studied the effect of cell crowding on protein diffusion, and found a relationship between protein size and the speed of diffusion. His team used three different prokaryotes with increasing ionic strength: the Gram-negative bacterium Escherichia coli (E coli), the Gram-positive Lactococcus lactis and the extremophile Haloferax volcanii, which lives in very high salt concentrations.

His researchers constructed different variations of Green Fluorescent Protein (GFP), with surface charges ranging from -30 to +25, and then studied their movement through the cell cytoplasm. 'We saw that positively charged proteins would diffuse very slowly. They got stuck in the cell", explains Poolman. Further analysis showed positive proteins didn't bind to DNA or the cell membrane but to the ribosome complex. The research appears in the journal eLife and attempts to explain why most water-soluble proteins, overall, carry a negative charge.

While investigating this relationship between a crowded cell cytoplasm, the ionic charge of molecular machinery inside that cytoplasm, and the proteins being created to be released into that cytoplasm, University of Groningen, Netherlands, biochemists made a fascinating discovery: positively charged proteins stick to the surface of ribosomes.

Water molecule
3D Model of Oxygen (red) (1) between 2 Hydrogen to form water molecule.
Image credit: Wikipedia

Ribosomes are molecular nano-machines where proteins are made. Found in all eukaryote or prokaryote cell types, they exist to link amino acids together as directed by mRNA. These protein chains go on to help build new cells and rebuild damaged ones.

Cells are composed mostly of water, plus inorganic ions, electrically charged atoms or groups of atoms, and carbon-containing (organic) molecules. As water is the most abundant molecule making up a cell, about 70% or more, interaction between water and other cell parts is extremely important.

Water's most important property is its polarity. Its two hydrogen (H) atoms have a slightly positive charge while its one oxygen (O) atom has a slightly negative charge. Because of this polarity, water molecules form hydrogen bonds not only with other water molecules, but with every other polar, or electrically charged molecules. Water also interacts with other positively or negatively charged ions. Therefore, ions and polar molecules are easily soluble in water. By contrast, nonpolar molecules cannot interact with water and tend to limit contacts within the cell to only other non-polar molecules.

Many molecules have enough energy to break noncovalent bonds. These bonds are so weak, they are sometimes referred to as interactions rather than bonds. Even so, many cell processes depend on interactions between proteins and nucleic acids, and on their ability to find each other. Research analysis showed that roughly 70 percent of those proteins were negatively charged. Poolman: "Interestingly, the remaining 30 percent are either membrane proteins or proteins involved in the function or folding of ribosomes or mRNA."

Cell membrane proteins are shielded by chaperones during cellular processes, so they won't stick to the ribosomes. Neither are there any free floating proteins in the cytoplasm with a positive charge high enough to make them stick to the ribosomes.
The negative charge given off by the ribosome complex and the ionic charge of cytoplasm, appear to shape the evolution of all protein charges expressed within a cell. This new and unexpected insight that protein mobility is the result of minute electrical charges - may explain why it is hard for some proteins to function in bacterial systems with low ionic strength.

Poolman: "We observed that a higher ionic strength reduces the stickiness of positively charged proteins. That could be a valuable insight for the construction of platforms for protein expression."

A final observation in the eLife paper is that genomes of several endosymbionts, such as mitochondria - an organism that lives in mutual benefit within the body or cells of another organism - have an abundance of positively charged proteins. Poolman: "This finding really baffles us. You would expect all these proteins to be attracted to the endosymbionts ribosomes. So far, we have no explanation of how these organisms are able to deal with slow diffusion and ribosomes being engulfed with positive proteins."

Much of the molecular motion in the cytoplasm is diffusive, which possibly limits the tempo of processes. We studied the dependence of protein mobility on protein surface properties and ionic strength. We used surface-modified fluorescent proteins (FPs) and determined their translational diffusion coefficients (D) in the cytoplasm of Escherichia coli, Lactococcus lactis and Haloferax volcanii. We find that in E. coli D depends on the net charge and its distribution over the protein, with positive proteins diffusing up to 100-fold slower than negative ones. This effect is weaker in L. lactis and Hfx. volcanii due to electrostatic screening. The decrease in mobility is probably caused by interaction of positive FPs with ribosomes as shown in in vivo diffusion measurements and confirmed in vitro with purified ribosomes. Ribosome surface properties may thus limit the composition of the cytoplasmic proteome. This finding lays bare a paradox in the functioning of prokaryotic (endo)symbionts.

Authors: Paul E Schavemaker Wojciech M ?migiel Bert Poolman

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Dec 7, 2017   Fetal Timeline   Maternal Timeline   News   News Archive

Positively charged ribosomes are molecular nano-machines where proteins are made.
Image credit: Wikipedia.

Phospholid by Wikipedia