Abstract
RecQ helicases feature multiple domains in their structure, of which the helicase domain, the RecQ-Ct domain and the HRDC domains are well conserved among the SF2 helicases. The helicase domain and the RecQ-Ct domain constitute the catalytic core of the enzyme. The domain interfaces are the DNA binding sites which display significant conformational changes in our molecular dynamics simulation studies. The preferred conformational states of the DNA bound and unbound forms of RecQ appear to be quite different from each other. DNA binding induces inter-domain flexibility leading to hinge mobility between the domains. The divergence in the dynamics of the two structures is caused by changes in the interactions at the domain interface, which seems to propagate along the whole protein structure. This could be essential in ssDNA binding after strand separation, as well as aiding translocation of the RecQ protein like an inch-worm.
Highlights
RecQ helicase is a member of the helicase superfamily 2 (SF2) [1,2]; it translocates in the 3' to 5' direction and contains the conserved DEAH box motif [3]
The helicase and RecQ-Ct domains together constitute the catalytic core of RecQ. In addition to these elements, eukaryotic RecQ proteins often contain N - and C - terminal extensions that confer additional functions like exonuclease domain in WRN, nuclear localization signals in BLM [9, 10] and the Zn finger and winged helix motifs in the RecQ-Ct domain [11].The complete structure of RecQ helicases has so far been resistant to attempts of crystallisation, so the X-ray structure is available for only two domains of the E.coli RecQ protein
We have adopted the homology modeling technique to construct the structure of the enzyme and carried out molecular dynamics (MD) simulations of the RecQ model and its DNA-docked complex to understand the mechanism of action of the protein
Summary
RecQ helicase is a member of the helicase superfamily 2 (SF2) [1,2]; it translocates in the 3' to 5' direction and contains the conserved DEAH box motif [3]. The helicase and RecQ-Ct domains together constitute the catalytic core of RecQ In addition to these elements, eukaryotic RecQ proteins often contain N - and C - terminal extensions that confer additional functions like exonuclease domain in WRN, nuclear localization signals in BLM [9, 10] and the Zn finger and winged helix motifs in the RecQ-Ct domain [11].The complete structure of RecQ helicases has so far been resistant to attempts of crystallisation, so the X-ray structure is available for only two domains of the E.coli RecQ protein. We have adopted the homology modeling technique to construct the structure of the enzyme and carried out molecular dynamics (MD) simulations of the RecQ model and its DNA-docked complex to understand the mechanism of action of the protein. MD simulations were carried out for E.coli RecQ and its DNA complex; the results provided insight into the mechanism by which the enzyme may function
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