Structure and function of hexameric helicases.
Helicases are motor proteins that couple the hydrolysis of nucleoside triphosphate (NTPase) to nucleic acid unwinding. The hexameric helicases have a characteristic ring-shaped structure, and all, except the eukaryotic minichromosomal maintenance (MCM) helicase, are homohexamers. Most of the 12 known hexameric helicases play a role in DNA replication, recombination, and transcription. A human genetic disorder, Bloom's syndrome, is associated with a defect in one member of the class of hexameric helicases. Significant progress has been made in understanding the biochemical properties, structures, and interactions of these helicases with DNA and nucleotides. Cooperativity in nucleotide binding was observed in many, and sequential NTPase catalysis has been observed in two proteins, gp4 of bacteriophage T7 and rho of Escherichia coli. The crystal structures of the oligomeric T7 gp4 helicase and the hexamer of RepA helicase show structural features that substantiate the observed cooperativity, and both are consistent with nucleotide binding at the subunit interface. Models are presented that show how sequential NTP hydrolysis can lead to unidirectional and processive translocation. Possible unwinding mechanisms based on the DNA exclusion model are proposed here, termed the wedge, torsional, and helix-destabilizing models.
Patel
S S
SS
Department of Biochemistry, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. patelss@UMDNJ.EDU
Picha
K M
KM
D017766:Acid Anhydride Hydrolases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017123:Bacteriophage T7 / Q000201:enzymology / Q000235:genetics; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D043583:Nucleoside-Triphosphatase; D020836:Protein Structure, Quaternary; D012313:RNA / Q000378:metabolism; D020365:RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D012313:RNA; D004247:DNA; D017766:Acid Anhydride Hydrolases; D043583:Nucleoside-Triphosphatase; D004265:DNA Helicases; D020365:RNA Helicases