title: Papillomavirus E1 helicase assembly maintains an asymmetric state in the absence of DNA and nucleotide cofactors.
abstract: Concerted, stochastic and sequential mechanisms of action have been proposed for different hexameric AAA+ molecular motors. Here we report the crystal structure of the E1 helicase from bovine papillomavirus, where asymmetric assembly is for the first time observed in the absence of nucleotide cofactors and DNA. Surprisingly, the ATP-binding sites adopt specific conformations linked to positional changes in the DNA-binding hairpins, which follow a wave-like trajectory, as observed previously in the E1/DNA/ADP complex. The protein's assembly thus maintains such an asymmetric state in the absence of DNA and nucleotide cofactors, allowing consideration of the E1 helicase action as the propagation of a conformational wave around the protein ring. The data imply that the wave's propagation within the AAA+ domains is not necessarily coupled with a strictly sequential hydrolysis of ATP. Since a single ATP hydrolysis event would affect the whole hexamer, such events may simply serve to rectify the direction of the wave's motion.
authors: Institute for Cancer Studies, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.
authors: Cyril M
authors: CM
authors: Sanders
authors: Oleg V
authors: OV
authors: Kovalevskiy
authors: Dmytro
authors: D
authors: Sizov
authors: Andrey A
authors: AA
authors: Lebedev
authors: Michail N
authors: MN
authors: Isupov
authors: Alfred A
authors: AA
authors: Antson
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D004265:DNA Helicases / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009711:Nucleotides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; C069814:E1 protein, Bovine papillomavirus; D009711:Nucleotides; D014764:Viral Proteins; D000255:Adenosine Triphosphate; D004247:DNA; D004265:DNA Helicases