Papillomavirus E1 helicase assembly maintains an asymmetric state in the absence of DNA and nucleotide cofactors

Cyril M. Sanders; Oleg V. Kovalevskiy; Dmytro Sizov; Andrey A. Lebedev; Michail N. Isupov; Alfred A. Antson

doi:10.1093/nar/gkm705

Papillomavirus E1 helicase assembly maintains an asymmetric state in the absence of DNA and nucleotide cofactors

Cyril M. Sanders, Oleg V. Kovalevskiy, Dmytro Sizov, Andrey A. Lebedev, Michail N. Isupov, Alfred A. Antson

Chemistry

Research output: Contribution to journal › Article › peer-review

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 proteins 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 waves 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 waves motion.

Original language	English
Pages (from-to)	6451-6457
Number of pages	7
Journal	Nucleic Acids Research
Volume	35
Issue number	19
DOIs	https://doi.org/10.1093/nar/gkm705
Publication status	Published - Oct 2007

Keywords

REPLICATIVE HEXAMERIC HELICASE
MOLECULAR-GRAPHICS
CRYSTAL-STRUCTURE
ATP HYDROLYSIS
TRANSLOCATION
MECHANISMS
E1

Access to Document

10.1093/nar/gkm705

Cite this

@article{17bac2771a4145028551342019e11199,

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 proteins 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 waves 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 waves motion.",

keywords = "REPLICATIVE HEXAMERIC HELICASE, MOLECULAR-GRAPHICS, CRYSTAL-STRUCTURE, ATP HYDROLYSIS, TRANSLOCATION, MECHANISMS, E1",

author = "Sanders, {Cyril M.} and Kovalevskiy, {Oleg V.} and Dmytro Sizov and Lebedev, {Andrey A.} and Isupov, {Michail N.} and Antson, {Alfred A.}",

year = "2007",

month = oct,

doi = "10.1093/nar/gkm705",

language = "English",

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journal = "Nucleic Acids Research",

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T1 - Papillomavirus E1 helicase assembly maintains an asymmetric state in the absence of DNA and nucleotide cofactors

AU - Sanders, Cyril M.

AU - Kovalevskiy, Oleg V.

AU - Sizov, Dmytro

AU - Lebedev, Andrey A.

AU - Isupov, Michail N.

AU - Antson, Alfred A.

PY - 2007/10

Y1 - 2007/10

N2 - 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 proteins 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 waves 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 waves motion.

AB - 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 proteins 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 waves 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 waves motion.

KW - REPLICATIVE HEXAMERIC HELICASE

KW - MOLECULAR-GRAPHICS

KW - CRYSTAL-STRUCTURE

KW - ATP HYDROLYSIS

KW - TRANSLOCATION

KW - MECHANISMS

KW - E1

U2 - 10.1093/nar/gkm705

DO - 10.1093/nar/gkm705

M3 - Article

SN - 0305-1048

VL - 35

SP - 6451

EP - 6457

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 19

ER -