The three-dimensional structure of the HRDC domain and implications for the werner and bloom syndrome proteins

Z. Liu, M. J. Macias, M. J. Bottomley, G. Stier, J. P. Linge, M. Nilges, P. Bork, M. Sattler

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

Background: The HRDC (helicase and RNaseD C-terminal) domain is found at the C terminus of many RecQ helicases, including the human Werner and Bloom syndrome proteins. RecQ helicases have been shown to unwind DNA in an ATP- dependent manner. However, the specific functional roles of these proteins in DNA recombination and replication are not known. An HRDC domain exists in both of the human RecQ homologues that are implicated in human disease and may have an important role in their function. Results: We have determined the three-dimensional structure of the HRDC domain in the Saccharomyces cerevisiae RecQ helicase Sgs1p by nuclear magnetic resonance (NMR) spectroscopy. The structure resembles auxiliary domains in bacterial DNA helicases and other proteins that interact with nucleic acids. We show that a positively charged region on the surface of the Sgs1p HRDC domain can interact with DNA. Structural similarities to bacterial DNA helicases suggest that the HRDC domain functions as an auxiliary domain in RecQ helicases. Homology models of the Werner and Bloom HRDC domains show different surface properties when compared with Sgs1p. Conclusions: The HRDC domain represents a structural scaffold that resembles auxiliary domains in proteins that are involved in nucleic acid metabolism. In Sgs1p, the HRDC domain could modulate the helicase function via auxiliary contacts to DNA. However, in the Werner and Bloom syndrome helicases the HRDC domain may have a role in their functional differences by mediating diverse molecular interactions.

Original languageEnglish
Pages (from-to)1557-1566
Number of pages10
JournalStructure
Volume7
Issue number12
DOIs
StatePublished - 15 Dec 1999
Externally publishedYes

Keywords

  • Bloom syndrome
  • HRDC domain
  • NMR
  • RecQ helicases
  • Werner syndrome

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