Structure-based model of the stepping motor of PcrA helicase

Jin Yu, Taekjip Ha, Klaus Schulten

Research output: Contribution to journalArticle

Abstract

DNA helicases are ubiquitous molecular motors involved in cellular DNA metabolism. They move along single-stranded DNA (ssDNA) and separate duplex DNA into its component strands, utilizing the free energy from ATP hydrolysis. The PcrA helicase from Bacillus stearothermophilus translocates as a monomer progressively from the 3′ end to the 5′ end of ssDNA and is one of the smallest motor proteins structurally known in full atomic detail. Using high-resolution crystal structures of the PcrA-DNA complex, we performed nanosecond molecular dynamics simulations and derived potential energy profiles governing individual domain movement of the PcrA helicase along ssDNA. Based on these profiles, the millisecond translocation of the helicase along ssDNA was described through Langevin dynamics. The calculations support a domain stepping mechanism of PcrA helicase, in which, during one ATP hydrolysis cycle, the pulling together and pushing apart of domains 2A and 1A are synchronized with alternating mobilities of the individual domains in such a fashion that PcrA moves unidirectionally along ssDNA. By combining short timescale (nanoseconds) molecular dynamics and long timescale (milliseconds) stochastic-dynamics descriptions, our study suggests a structure-based mechanism of the ATP-powered unidirectional movement of PcrA helicase.

Original languageEnglish (US)
Pages (from-to)2097-2114
Number of pages18
JournalBiophysical Journal
Volume91
Issue number6
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Single-Stranded DNA
Adenosine Triphosphate
Molecular Dynamics Simulation
DNA
Hydrolysis
DNA Helicases
Geobacillus stearothermophilus
Proteins

ASJC Scopus subject areas

  • Biophysics

Cite this

Structure-based model of the stepping motor of PcrA helicase. / Yu, Jin; Ha, Taekjip; Schulten, Klaus.

In: Biophysical Journal, Vol. 91, No. 6, 2006, p. 2097-2114.

Research output: Contribution to journalArticle

Yu, Jin ; Ha, Taekjip ; Schulten, Klaus. / Structure-based model of the stepping motor of PcrA helicase. In: Biophysical Journal. 2006 ; Vol. 91, No. 6. pp. 2097-2114.
@article{e5068c9fd3484ded8b12800300c72c05,
title = "Structure-based model of the stepping motor of PcrA helicase",
abstract = "DNA helicases are ubiquitous molecular motors involved in cellular DNA metabolism. They move along single-stranded DNA (ssDNA) and separate duplex DNA into its component strands, utilizing the free energy from ATP hydrolysis. The PcrA helicase from Bacillus stearothermophilus translocates as a monomer progressively from the 3′ end to the 5′ end of ssDNA and is one of the smallest motor proteins structurally known in full atomic detail. Using high-resolution crystal structures of the PcrA-DNA complex, we performed nanosecond molecular dynamics simulations and derived potential energy profiles governing individual domain movement of the PcrA helicase along ssDNA. Based on these profiles, the millisecond translocation of the helicase along ssDNA was described through Langevin dynamics. The calculations support a domain stepping mechanism of PcrA helicase, in which, during one ATP hydrolysis cycle, the pulling together and pushing apart of domains 2A and 1A are synchronized with alternating mobilities of the individual domains in such a fashion that PcrA moves unidirectionally along ssDNA. By combining short timescale (nanoseconds) molecular dynamics and long timescale (milliseconds) stochastic-dynamics descriptions, our study suggests a structure-based mechanism of the ATP-powered unidirectional movement of PcrA helicase.",
author = "Jin Yu and Taekjip Ha and Klaus Schulten",
year = "2006",
doi = "10.1529/biophysj.106.088203",
language = "English (US)",
volume = "91",
pages = "2097--2114",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "6",

}

TY - JOUR

T1 - Structure-based model of the stepping motor of PcrA helicase

AU - Yu, Jin

AU - Ha, Taekjip

AU - Schulten, Klaus

PY - 2006

Y1 - 2006

N2 - DNA helicases are ubiquitous molecular motors involved in cellular DNA metabolism. They move along single-stranded DNA (ssDNA) and separate duplex DNA into its component strands, utilizing the free energy from ATP hydrolysis. The PcrA helicase from Bacillus stearothermophilus translocates as a monomer progressively from the 3′ end to the 5′ end of ssDNA and is one of the smallest motor proteins structurally known in full atomic detail. Using high-resolution crystal structures of the PcrA-DNA complex, we performed nanosecond molecular dynamics simulations and derived potential energy profiles governing individual domain movement of the PcrA helicase along ssDNA. Based on these profiles, the millisecond translocation of the helicase along ssDNA was described through Langevin dynamics. The calculations support a domain stepping mechanism of PcrA helicase, in which, during one ATP hydrolysis cycle, the pulling together and pushing apart of domains 2A and 1A are synchronized with alternating mobilities of the individual domains in such a fashion that PcrA moves unidirectionally along ssDNA. By combining short timescale (nanoseconds) molecular dynamics and long timescale (milliseconds) stochastic-dynamics descriptions, our study suggests a structure-based mechanism of the ATP-powered unidirectional movement of PcrA helicase.

AB - DNA helicases are ubiquitous molecular motors involved in cellular DNA metabolism. They move along single-stranded DNA (ssDNA) and separate duplex DNA into its component strands, utilizing the free energy from ATP hydrolysis. The PcrA helicase from Bacillus stearothermophilus translocates as a monomer progressively from the 3′ end to the 5′ end of ssDNA and is one of the smallest motor proteins structurally known in full atomic detail. Using high-resolution crystal structures of the PcrA-DNA complex, we performed nanosecond molecular dynamics simulations and derived potential energy profiles governing individual domain movement of the PcrA helicase along ssDNA. Based on these profiles, the millisecond translocation of the helicase along ssDNA was described through Langevin dynamics. The calculations support a domain stepping mechanism of PcrA helicase, in which, during one ATP hydrolysis cycle, the pulling together and pushing apart of domains 2A and 1A are synchronized with alternating mobilities of the individual domains in such a fashion that PcrA moves unidirectionally along ssDNA. By combining short timescale (nanoseconds) molecular dynamics and long timescale (milliseconds) stochastic-dynamics descriptions, our study suggests a structure-based mechanism of the ATP-powered unidirectional movement of PcrA helicase.

UR - http://www.scopus.com/inward/record.url?scp=33748335314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748335314&partnerID=8YFLogxK

U2 - 10.1529/biophysj.106.088203

DO - 10.1529/biophysj.106.088203

M3 - Article

C2 - 16815905

AN - SCOPUS:33748335314

VL - 91

SP - 2097

EP - 2114

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 6

ER -