title: A Brownian motor mechanism of translocation and strand separation by hepatitis C virus helicase.
abstract: Helicases translocate along their nucleic acid substrates using the energy of ATP hydrolysis and by changing conformations of their nucleic acid-binding sites. Our goal is to characterize the conformational changes of hepatitis C virus (HCV) helicase at different stages of ATPase cycle and to determine how they lead to translocation. We have reported that ATP binding reduces HCV helicase affinity for nucleic acid. Now we identify the stage of the ATPase cycle responsible for translocation and unwinding. We show that a rapid directional movement occurs upon helicase binding to DNA in the absence of ATP, resulting in opening of several base pairs. We propose that HCV helicase translocates as a Brownian motor with a simple two-stroke cycle. The directional movement step is fueled by single-stranded DNA binding energy while ATP binding allows for a brief period of random movement that prepares the helicase for the next cycle.
authors.affiliation: UMDNJ-Robert Wood Johnson Medical School, Department of Biochemistry, 675 Hoes Lane, Piscataway, New Jersey 08854, USA.
authors.forename: Mikhail K
authors.initials: MK
authors.lastname: Levin
authors.forename: Madhura
authors.initials: M
authors.lastname: Gurjar
authors.forename: Smita S
authors.initials: SS
authors.lastname: Patel
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D016174:Hepacivirus / Q000201:enzymology* / Q000235:genetics; D007700:Kinetics; D008954:Models, Biological; D021381:Protein Transport; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D004247:DNA; D020365:RNA Helicases; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases