Helicase mechanisms and the coupling of helicases within macromolecular machines. Part I: Structures and properties of isolated helicases.
Helicases are proteins that harness the chemical free energy of ATP hydrolysis to catalyze the unwinding of double-stranded nucleic acids. These enzymes have been much studied in isolation, and here we review what is known about the mechanisms of the unwinding process. We begin by considering the thermally driven 'breathing' of double-stranded nucleic acids by themselves, in order to ask whether helicases might take advantage of some of these breathing modes. We next provide a brief summary of helicase mechanisms that have been elucidated by biochemical, thermodynamic, and kinetic studies, and then review in detail recent structural studies of helicases in isolation, in order to correlate structural findings with biophysical and biochemical results. We conclude that there are certainly common mechanistic themes for helicase function, but that different helicases have devised solutions to the nucleic acid unwinding problem that differ in structural detail. In Part II of this review (to be published in the next issue of this journal) we consider how these mechanisms are further modified to reflect the functional coupling of these proteins into macromolecular machines, and discuss the role of helicases in several central biological processes to illustrate how this coupling actually works in the various processes of gene expression.
Delagoutte
Emmanuelle
E
Institute of Molecular Biology, Department of Chemistry, University of Oregon, Eugene, OR 97403, USA.
von Hippel
Peter H
PH
D020029:Base Pairing; D004265:DNA Helicases / Q000737:chemistry* / Q000145:classification; D004795:Enzyme Stability; D046911:Macromolecular Substances; D020409:Molecular Motor Proteins / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry* / Q000145:classification; D012330:RNA, Double-Stranded / Q000737:chemistry*; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; D020409:Molecular Motor Proteins; D012330:RNA, Double-Stranded; D004265:DNA Helicases; D020365:RNA Helicases