3D Structure of HRDC domain of RecQ Helicase

CPK Color Scheme
 C O N P S

RecQ Helicases are a family of 3'-5' exonucleases that maintain genomic stability. Mutations in RecQ Helicases can cause Bloom's, Werner's, or Rothmund-Thomson Syndrome. RecQ Helicases share highly conserved domains, including the Helicase RNaseD C-terminus domain, or the HRDC domain.

Click here to learn more about the RecQL3 Helicase involved in Bloom's syndome

BLM gene encodes RecQ Helicase


This tutorial describes the structure of the HRDC domain. The HRDC domain is thought to contribute to the auxiliary molecular interactions of RecQ Helicases by binding with DNA in a non-specific manner.
Reset the structure of HRDC.

The HRDC domain consists of 80 amino acids and is found at the C-terminus of RecQ Helicases and other RNAseD homologs. The HRDC domain is composed of five distinct alpha helices.

Like many structurally independent protein domains, the N and C termini of HRDC are in close spatial proximity.
The N-terminus of the protein is shown in light blue.
The C-terminus of the protein is shown in light blue.

The N-terminus alpha helices 1 and 2 are connected by a long hydrophobic loop (shown in red).

The four amino acid stretch of Val34-Pro35-Pro36-Val37 (shown in yellow) is especially conserved in the hydrophobic loop of the HRDC domain across species. It is likely that this region is involved in intramolecular or intermolecular interactions in the RecQ Helicase proteins.

Short turns connect alpha helices 2 and 3 and alpha helices 3 and 4 (red).

Alpah helices 4 and 5 are connected by Lysine75 in a 60 degree turn (red).

The conserved hydrophobic residues in the alpha helices contribute to the hydrophobic core and thus the turns between helices and structure of the HRDC domain. Most notably, Leu22, Leu46, Met49, Phe60, Leu63, and Phe74 (all in orange) are the higly conserved residues that are responsible for maintaining a common folding pattern for all HRDC domains.

The HRDC domain is very positively charged because of the presence of lysines (green) and arginines (yellow).

Of the positively charged residues, Lys69 (green) is the most highly conserved across species. Because many of the residues vary for each protein, the positive charge of the HRDC domain also varies. The differences in the HRDC domain are thought to contribute to the differences in function between BLM, WRN, and other RecQ Helicases.

The HRDC domain is known to interact with DNA in a non-sequence specific manner. A basic patch of the HRDC domain that has a low DNA binding affinity comes in contact with the phosphate backbone of DNA. The residues (shown in magenta) of alpha helix 4 and the C-terminus end of alpha helix 1 have the strongest interactions with DNA. Because the basic patch can interact with multiple DNA ligands, the HRDC domain contributes to the auxiliary molecular interactions in RecQ Helicases such as the positioning of the helicase substrates.


References

Kogoy, John. 2003. Chime Tutorial Manual. Accessed 2003, April 8.

Liu, Z. et al. 1999. The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins. Structure 7: 1557-1566.

Protein Data Bank. 2003. Structure Explorer 1D8B. http://www.pdb.org. Accessed 2003 April 8.