PcrA helicase, a prototype ATP-driven molecular motor.
Despite extensive studies, the mechanisms underlying molecular motor function are still poorly understood. Key to the mechanisms is the coupling of ATP hydrolysis to conformational changes of the motor protein. To investigate this coupling, we have conducted combined quantum mechanical/molecular mechanical simulations of PcrA helicase, a strikingly simple motor that translocates unidirectionally along single-stranded DNA (ssDNA). Our results reveal a close similarity in catalytic site structure and reaction pathway to those of F1-ATPase, and these similarities include a proton relay mechanism important for efficient ATP hydrolysis and an "arginine finger" residue that is key to the coupling of the chemical reaction to protein conformational changes. By means of in silico mutation studies, we identified the residue Q254 as being crucial for the coupling of ssDNA translocation to the actual catalytic event. Based on the present result for PcrA helicase and previous findings for F1-ATPase, we propose a general mechanism of ATP-driven molecular motor function.
Dittrich
Markus
M
Theoretical and Computational Biophysics Group, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Schulten
Klaus
K
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D006868:Hydrolysis; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D006180:Proton-Translocating ATPases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D004277:DNA, Single-Stranded; D020409:Molecular Motor Proteins; C084217:pcrA protein, Bacteria; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D004265:DNA Helicases