BIOPHYSICAL THEORY AND MODELING |
Structure-based Model of the Stepping Motor of PcrA Helicase
Jin Yu 1, Taekjip Ha 2 and Klaus Schulten 1*
1 University of Illinois at Urbana-Champaign
2 University of Illinois at Urbana-Champaign; Howard Hughes Medical Institute, Urbana
* To whom correspondence should be addressed. E-mail: kschulte{at}ks.uiuc.edu.
Submitted on April 28, 2006
Revised on May 30, 2006
Accepted on 13 June 2006
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Abstract |
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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 time-scale (nanoseconds) molecular dynamics and long time-scale (milliseconds) stochastic dynamics descriptions, our study suggests a structure-based mechanism of the ATP-powered unidirectional movement of PcrA helicase.
Key Words:
ATP hydrolysis, DNA helicase, PcrA, molecular dynamics simulation, molecular motor, stochastic modeling
