Jmol Tutorial of Telomerase

CPK Color Scheme

The 3D structure rotating to the left shows the TERT protein, which is the catalytic subunit found in telomerase. Telomerase is involved in extending the telomeres by adding DNA to the ends of chromosomes using an RNA template. Telomerase is essential in eukaryotes given that the telomeres gradually shorten with age due to problems with the replication of linear DNA.

Reset and rotate the molecule.

TERT can be either a monomer or a dimer and still retain its activity. The green and blue regions indicate the two TERT monomers. Notice that the monomers have exactly the same structure but are organized in opposite orientations.

Examine the overall shape of the TERT monomer. It forms a doughnut-like ring to accommodate incoming strands of DNA and the RNA template in the center of the protein. The slab animation reveals the center of the molecule, which is where the reaction will take place. This ring shape is similar to that of the reverse transcriptase family.

Look at the various domains of the protein. The coloring roughly corresponds with the domains of the TERT protein from the amino terminal in blue to the carboxy terminal in red. The blue portion is the TRBD domain, the green region is the thumb domain and the yellow-orange region is the palm and fingers regions of the protein. Excluding the TRBD domain, this domain organization is similar to the structure of reverse transcriptase.

Now view the secondary structure. Notice the abundance of alpha helices (in pink) and the relative absence of beta strands (in yellow). The alpha helices are integral in interacting with the grooves of the RNA/DNA double helix.

There are three lysine residues in red and an arginine residue in purple located at the center of the TERT protein . These positively charged residues will interact with and stabilize the negatively charged backbone of the DNA template. They appear to form part of a spiral, which follows the DNA double helix model.

Now let's look at the active site. It has been shown that there are three aspartic acids that are conserved among species and are necessary for TERT activity. Not surprisingly, these amino acids are located in the interior of the ring where they can bind nucleotides to the growing strand of DNA.

Thanks for viewing my jmol tutorial on telomerase!

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