Nucleotide-protein interactions

Unlike protein-protein and nucleotide-protein interactions, progress in understanding the role... 

Protein-protein interactions predicted on the sequence level can be studied in more detail on the structure level. Single Nucleotide Polymorphisms can be mapped on 3D structures of proteins in order to elucidate specific structural causes of disease. 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

Exonuclease III j Removes nucleotides from 3 ends of DNA. DNA sequencing mapping of DNA-protein interactions. 

G-proteins are molecular timers that couple transmembrane receptor activation to downstream members of the pathway (Fig. 9-5). They are called G-proteins because they are intimately involved with the nucleotide, GTP. Before activation, the G-protein is hanging around in its GDP form. When the activated receptor finds its G-protein it activates it by increasing the rate of exchange between GTP and GDP. Once activated, the G-protein interacts with downstream effectors and can activate... 

Treatment with hot organic solvents was the next step in the tissue fractionation, to remove lipid-phosphorous and breakdown lipid-protein interactions. In the Schneider procedure, nucleic acids were then extracted in hot dilute trichloroacetic or perchloric acid, leaving a protein residue with any phosphoprotein links still intact. This method was to become particularly useful when 3H thymidine became the preferred label for DNA in the early 1960s. For investigations where both RNA and DNA were to be examined the Schmidt-Thannhauser process was often chosen. Here the lipid-extracted material was hydrolyzed with dilute sodium hydroxide releasing RNA nucleotides and any hydroxyamino acid bound phosphorus. DNA could be precipitated from the extract but the presence in the alkaline hydrolysate of the highly labeled phosphate released from phosphoprotein complicated... 

In addition to its influence on protein—protein interactions, phosphorylation also affects protein structure and activity. One case involves a protein termed dematin headpiece (DHP), an actin-binding protein found in a variety of tissues including heart, brain, skeletal muscle, kidney, and lung." DHP is known to interact with Ras-guanine nucleotide exchange factor (Ras-GRF2) and this interaction can modulate MARK pathways, which can link the cytoskeleton and signaling pathways." ... 

In the membrane-localized form, Sos protein interacts with Ras protein, which is also membrane associated, and induces nucleotide exchange in the latter. It is assumed that relocation of the Grb2-Sos complex from the cytosol to the membrane is the decisive step that establishes binding between the activated receptor and Ras protein. The membrane association of both proteins is sufficient for activation of signal transduction and to switch on the Ras protein, according to this assumption. 

One of the problems with DNA is that it is essentially a linear code that stores information. The functional groups (nucleotides) only interact with each other and, while this can lead to the elegant double helix, it limits the ability of DNA to form different secondary and extensive tertiary structures. RNA is rather more amenable to forming other structural motifs, hence the RNA World theory of molecular evolution, but it appears that only proteins with their varied side chains are able to adopt truly complex structures. 

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