Vacuolar ATPases (V-ATPases) function as proton pumps in many cellular processes such as cancer metastasis and bone resorption, and are thus attractive drug targets for cancer and osteoporosis. The hydrophilic V1 portion is known as a rotary motor powered by energy from ATP hydrolysis. Prof. Murata’s group at Chiba University recently reported the crystal structures of the Enterococcus hirae V1-ATPase, corresponding to the catalytic dwell state waiting for ATP hydrolysis. However, the rotation mechanism after ATP hydrolysis was unclear.
The research group presented the crystal structures for two other dwell states, corresponding to the ATP-binding and ADP-release dwells, obtained by soaking nucleotide-free V1 crystals in ADP. Based on these and previous findings, the group proposed a V1-ATPase rotational mechanism model.
Research Area “Structural science and advanced core technologies for innovative life science research”
Research Theme “Elucidation of molecular mechanism of the nano-molecular rotary motor by correlative structural analyses”
Kano Suzuki, Kenji Mizutani, Shintaro Maruyama, Kazumi Shimono, Fabiana L. Imai, Eiro Muneyuki, Yoshimi Kakinuma, Yoshiko Ishizuka-Katsura, Mikako Shirouzu, Shigeyuki Yokoyama, Ichiro Yamato, and Takeshi Murata. “Crystal structures of the ATP-binding and ADP-release dwells of the V1 rotary motor”. Nature Communications 7, Published online 27 October 2016, doi: 10.1038/ncomms13235.
Takeshi Murata, Ph.D.
Professor, Department of Chemistry, Graduate School of Science, Chiba University
Life Innovation Group, Department of Innovation Research, JST