BIOPHYSICAL THEORY AND MODELING |
How Directional Translocation is Regulated in a DNA Helicase Motor
Jin Yu 1, Taekjip Ha 1 and Klaus Schulten 1*
1 University of Illinois at Urbana-Champaign
* To whom correspondence should be addressed. E-mail: kschulte{at}ks.uiuc.edu.
Submitted on March 24, 2007
Revised on May 20, 2007
Accepted on 18 July 2007
 |
Abstract |
|---|
PcrA helicase from Bacillus stearothermophilus is one of the smallest motor proteins structurally known in full atomic detail. It translocates progressively from the 3' end to the 5' end of ssDNA utilizing the free energy from ATP hydrolysis. The similarities of structure and reaction pathway between PcrA helicase and F1 ATPase suggest a similar mechanochemical mechanism at work in both systems. Previous studies of PcrA translocation demonstrated a domain stepping mechanism in which, during one ATP hydrolysis cycle, the pulling together and pushing apart of two translocation domains is synchronized with alternating mobilities of the individual domains such that PcrA moves unidirectionally along ssDNA. To substantiate this translocation mechanism, the present study applies molecular dynamics simulations, elastic network theory, and multiple sequence alignment to analyze the system. The analyses provide further evidence for directional translocation of PcrA being regulated allosterically through synchronization of ATP hydrolysis and domain mobilities. A set of essential residues coevolutionarily coupled in related helicases are identified that should be involved in the allosteric regulation of these motor proteins.
Key Words:
ATP Hydrolysis, Coevolutionary Analysis, DNA Helicase, Elastic Network Model, Molecular Dynamics Simulation
