RGG Box
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The arginine-glycine or arginine-glycine-glycine (RG/RGG) motif is a repeating
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
sequence motif In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ''A ...
commonly found in
RNA-binding protein RNA-binding proteins (often abbreviated as RBPs) are proteins that bind to the double or single stranded RNA in cell (biology), cells and participate in forming ribonucleoprotein complexes. RBPs contain various structural motifs, such as RNA reco ...
s (RBPs). RGG regions in proteins are defined as two or more RG/RGG sequences within a stretch of 30 amino acids. Initially named the RGG box, it confers a protein with the ability to bind double-stranded mRNA molecules. The RGG motif has been observed in proteins from at least 12 animal species, including humans.


Biochemical function

RGG motifs are primarily involved in mediating protein-RNA interactions. Positive charges from
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
residues promote
electrostatic interactions Electrostatics is a branch of physics that studies slow-moving or stationary electric charges. Since classical times, it has been known that some materials, such as amber, attract lightweight particles after rubbing. The Greek word (), meani ...
with mRNA molecules. The composition and structure of the arginine side chain may also allow for specific interactions with other molecules as opposed to the other positively charged
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s, lysine and histidine. Glycine residues add flexibility to the peptide structure and promote their tendency to form intrinsically disordered regions. The RGG motif can also drive liquid-lipid phase separation of proteins inside cells as well as ''in vitro.''


Synthetic uses

Researchers have pursued creating condensates with novel functions for use in cellular and
metabolic engineering Metabolic engineering is the practice of optimizing genetic and regulatory processes within cells to increase the cell's production of a certain substance. These processes are chemical networks that use a series of biochemical reactions and enzy ...
. Synthetically designed proteins containing repeating RGG motifs have been used to form droplets with tunable properties in cells and ''in vitro.''


Notable RGG-containing proteins

RGG motif-containing proteins are the second most abundant group of RBPs in the human genome. They are involved in various RNA metabolism, export, and translation functions. * Sbp1 * Npl3 * Ded1 *
FMR1 ''FMR1'' (Fragile X Messenger Ribonucleoprotein 1) is a human gene that codes for a protein called ''fragile X messenger ribonucleoprotein'', or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive developmen ...
* FUS * Laf-1


References

{{reflist Bioinformatics