3D Structure of HIV Reverse Transcriptase

CPK Color Scheme

On this page, you can see the HIV reverse transcriptase protein. Notice that it is a heterodimeric protein.
Reset and spin the HIV reverse transcriptase protein.

Notice the catalytic site of this protein, which is located in the p66 subunit and is highly conserved across many species (YXDD). This open hole is the region where there is a conformational change in the shape of the protein such that the substrate (RNA) can bind to this protein and a DNA chain can be polymerized.

Look at the aspartic acid residues that interact with the phosphate groups on incoming nucleotide triphosphates. Notice how close they are to the catalytic site of the protein. Two of the three aspartic acid residues are actually part of the catalytic site, whereas the third is not. Notice, however, that even the aspartic acid residue that is not part of the catalytic is located very close to the YXDD box.

Look at the amino acid residues responsible for holding the RNA template strand in place. Notice how close the catalytic site (seen in button 2) and the aspartic acid residues (seen in button 3) are to these residues.

Notice the tyrosine amino acid residue that is responsible for interacting with the nucleotide being added to the growing DNA strand. Notice the relationship of this residue to the catalytic site in button 2.

Look at the catalytic subunit of this protein (p66) colored in purple and the p51 subunit (colored in green). The p51 subunit is important for tRNA binding (which is the primer for HIV-1 reverse transcriptase) and for stabilizing the p66 subunit.

Look at the fingers (red), palm (green), and thumb (blue) domains. All of these domains together make up the DNA polymerase domain. You will notice that these domains are present in both the p51 and p66 subunits, but DNA polymerase activity only occurs in the p66 domain. The thumb domain is the region of this protein that moves in order to allow for the RNA template strand to interact with the reverse transcriptase. The connection domain (yellow) is where the two subunits connect to each other and is responsible for binding the primer template (Kohlstaedt et al., 1992). The RNase H domain (brown) is only found in the p66 subunit and it is responsible for chewing up the RNA template strand after DNA has been synthesized. Also look at the secondary structure of this protein and the distribution of alpha helices and beta sheets throughout the protein. Notice how the alpha helices and beta pleated sheets are oriented differently in p66 and p51 subunits even though the p51 subunit is made up of the first 450 amino acids of the p66 subunit.

Notice the seven highly conserved domains among reverse transcriptase proteins. The catalytic domain (colored in blue), is the only domain that is completely conserved across all species. The other domains discussed in this tutorial (the aspartic acid residues, the amino acid residues responsible for holding the RNA template strand in place and the tyrosine residue) are not highly conserved across species. In addition, notice how all of the conserved domains are located very close to the catalytic site in the p66 domain.

All of the reference information regarding this tutorial can be found on the structure-function and orthologs pages that are linked from Pallavi's Home Page. The papers regarding the information about where the palm, fingers, thumb, connection and RNase H domains are located on the HIV-1 reverse transcriptase structure and function page.
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