Publications (2)19.36 Total impact
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Article: Dynamic flexibility of the ATPase p97 is important for its interprotomer motion transmission.
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ABSTRACT: The hexameric protein p97, a very abundant type II AAA ATPase (ATPase associated with various cellular activities), is involved in a diverse range of cellular functions. During its ATPase cycle p97 functions as an ATP motor, converting the chemical energy released upon hydrolysis of ATP to ADP into mechanical work, which is then directed toward the proteins that serve as substrates. A key question in this process is: How is the nucleotide-induced motion transmitted from the C-terminal ATPase domain (the D2 domain) of p97 to the distant N-terminal substrate-processing domain? We have previously reported the surprising finding that motion transmission between the two ATPase domains (the D2 and D1 domains) is mediated by the D1-D2 linker region of its neighboring protomer. In this study we report efforts to better understand this process. Our findings suggest that the amino acid sequence containing Gly-Gly that is located at the C terminus of the D1-D2 linker functions as a pivoting point that allows the dynamic movement of the D1-D2 linker. Furthermore, we found that locking the D1-D2 linker to the D2 domain by introducing disulfide bonds significantly impaired the motion-transmission process. These results support our previous model for interprotomer motion transmission, and provide more detailed information on how the motion transmission between the two ATPase domains of p97 is relayed by the flexible movement of the D1-D2 linker from its neighboring protomer.Proceedings of the National Academy of Sciences 06/2012; 109(25):9792-7. · 9.68 Impact Factor -
Article: Interprotomer motion-transmission mechanism for the hexameric AAA ATPase p97.
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ABSTRACT: Multimeric AAA ATPases represent a structurally homologous yet functionally diverse family of proteins. The essential and highly abundant hexameric AAA ATPase p97 is perhaps the best studied AAA protein, playing an essential role in various important cellular activities. During ATP-hydrolysis process, p97 undergoes dramatic conformational changes, and these changes are initiated in the C-terminal ATPase domain and transmitted across the entire length of the molecule to the N-terminal effector domain. However, the detailed mechanism of the motion transmission remains unclear. Here, we report an interprotomer motion-transmission mechanism to explain this process: The nucleotide-dependent motion transmission between the two ATPase domains of one protomer is mediated by its neighboring protomer. This finding reveals a strict requirement for interprotomer coordination of p97 during the motion-transmission process and may shed light on studies of other AAA ATPases.Proceedings of the National Academy of Sciences 03/2012; 109(10):3737-41. · 9.68 Impact Factor
