Helicase motifs: the engine that powers DNA unwinding

Abstract

SummaryHelicases play essential roles in nearly all DNA metabolic transactions and have been implicated in a variety of human genetic disorders. A hallmark of these enzymes is the existence of a set of highly conserved amino acid sequences termed the`helicase motifs' that were hypothesized to be critical for helicase function. These motifs are shared by another group of enzymes involved in chromatin remodelling. Numerous structure±function studies, targeting highly conserved residues within the helicase motifs, have been instrumental in uncovering the functional signi®-cance of these regions. Recently, the results of these mutational studies were augmented by the solution of the three-dimensional crystal structure of three different helicases. The structural model for each helicase revealed that the conserved motifs are clustered together, forming a nucleotide-binding pocket and a portion of the nucleic acid binding site. This result is gratifying, as it is consistent with structure±func-tion studies suggesting that all the conserved motifs are involved in the nucleotide hydrolysis reaction. Here, we review helicase structure±function studies in the light of the recent crystal structure reports. The current data support a model for helicase action in which the conserved motifs de®ne an engine that powers the unwinding of duplex nucleic acids, using energy derived from nucleotide hydrolysis and conformational changes that allow the transduction of energy between the nucleotide and nucleic acid binding sites. In addition, this ATP-hydrolysing engine is apparently also associated with proteins involved in chromatin remodelling and provides the energy required to alter protein-DNA structure, rather than duplex DNA or RNA structure.

Identification of genes that are associated with DNA repeats in prokaryotes

“…The amino acid sequences of the Cas3 proteins contain the seven motifs that are characteristic for the superfamily 2 of the helicases, proteins that power DNA unwinding. Homologues of this superfamily may have functions in DNA repair, transcriptional regulation, chromosome segregation, recombination and chromatin remodelling (Hall and Matson, 1999). The Cas4 proteins showed similarity to RecB exonucleases.…”

TraA is required for megaplasmid conjugation in Rhodococcus erythropolis AN12

“…In addition, this region is 27% identical to TraA relaxase/helicase encoded by the Agrobacterium tumefaciens pTiC58 plasmid (Farrand et al, 1996), and 22% identical to the TraI relaxase/helicase of the E. coli F factor (AbdelMonem et al, 1983;Larkin et al, 2005;Street et al, 2003). Alignments to the consensus helicase motifs (Hall and Matson, 1999) revealed that pREA400 TraA and its actinomycete relatives belong to the superfamily I (SFI) type of helicases (Fig. 3A).…”

“…Protein alignments of DNA helicase and relaxase domains of pREA400 TraA. (A) Alignments of actinomycete transfer proteins from the indicated strains or plasmids to the consensus motifs (I, IA, II, III, IV, V, and VI) of superfamily I-type helicases (Hall and Matson, 1999). Consensus hydrophobic, hydrophilic and non-speciWc helicase residues are indicated with +, o, and x, respectively.…”

Erratum to: Structure and Mechanisms of SF1 DNA Helicases

“…This motif, DExx, is involved in NTP hydrolysis [46,76,86]. The D and E residues coordinate the ATP-associated Mg 2+ and activate the attacking water molecule, respectively [109,110].…”