Decapping complex

There are many proteins that stay the same, but several key differences between the single-celled (yeast) and multicellular (metazoan) decapping complexes.

[5] In yeast (S. cerevisiae), Dcp2 is joined by the decapping activator Dcp1, the helicase Dhh1, the exonuclease Xrn1, nonsense mediated decay factors Upf1, Upf2, and Upf3, the LSm complex, Pat1, and various other proteins.

The enzyme Dcp2 is still the catalytic subunit which forms a holoenzyme with Dcp1, and interacts with auxiliary proteins such as Xrn1, Upf1, Upf2, Upf3, the LSm complex, and the Dhh1 ortholog DDX6.

Dcp2, as the main catalyst of the decapping process, relies on a specific pattern of amino acids called a nudix domain to align itself with the 5' cap in order to hydrolyze it.

[5] A nudix domain is made by packing two beta sheets between multiple alpha helices, can be various lengths and sizes, and is generally used by proteins to carry out dephosphorylation, getting rid of a phosphate by inserting a water molecule into the bond between the phosphate and the rest of the molecule.

[10] In the case of Dcp2, it contains multiple glutamic acid side chains that are negatively charged in normal cellular conditions, and these are what allow the protein to manipulate water molecules to hydrolyze the tri-phosphate bridge that connects the 5' end of the mRNA to the 7-methylguanosine cap.

[5] Therefore, the nudix domain is what allows Dcp2 to remove the 5' cap, which results in the creation 7mGDP, a 7-methylguanosine with two phosphate groups attached, and a monophosphorylated mRNA strand.

The domain that recognises PRS is made of mostly hydrophobic amino acids, and is found within the cleft of the 'V' of the Dcp1 structure.

Current research suggests PNRC2 helps associate Dcp2 and Dcp1 together, making the Dcp2-Dcp1 holoenzyme more stable and therefore increasing the effectiveness of Dcp2, but the exact details about how it does so are vague.

[14] It is proposed that, since it is a helicase, it is involved in reconfiguring the 5' end of the mRNA to give Dcp2 easier access to the 5' cap, and that it stimulates Dcp1 so that it interacts better with Dcp2 when attached to the rest of the decapping complex.

It possesses an LSm domain at its N-terminus, which interacts with specific amino acid motifs called HLM fragments which are found on the C terminus of Dcp1 and allows for Edc3 to bind to it.

The other two make it easier for the protein to decap mRNA, but are not directly involved in the hydrolysis of the phosphate bond.

The chemical structure of the 5’ capped mRNA, with labeled portions that indicate where several key structures involved with decapping mRNA are.
The chemical structure of capped mRNA, showing how the decapping complex interacts with the 5’ cap. It is the Dcp2 enzyme, specifically its Nudix domain, that hydrolyzes a phosphate bond and removes the cap.
The chemical structure of monophosphorylated mRNA, which is what is left over when the decapping complex removes the 5’ cap and removes 7mGDP from the rest of the mRNA.